PDBsum entry 1n2r

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Immune system PDB id
Protein chains
276 a.a. *
99 a.a. *
ACY ×2
Waters ×481
* Residue conservation analysis
PDB id:
Name: Immune system
Title: A natural selected dimorphism in hla b 44 Alters self, peptide reportoire and t cell recognition.
Structure: Hla class i histocompatibility antigen, bw-44(b- 12) b 4403 Alpha chain. Chain: a. Engineered: yes. Other_details: truncated b 4403 Heavy chain. Beta-2-microglobulin. Chain: b. Synonym: hdcma22p. Engineered: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-b or hlab. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Gene: b2m. Synthetic: yes. Other_details: the protein was chemically synthesized. The
Biol. unit: Trimer (from PQS)
1.70Å     R-factor:   0.229     R-free:   0.261
Authors: W.A.Macdonald,A.W.Purcell,D.S.Williams,N.Mifsud,L.K.Ely, J.J.Gorman,C.S.Clements,L.Kjer-Nielsen,D.M.Koelle, A.G.Brooks,G.O.Lovrecz,L.Lu,J.Rossjohn,J.Mccluskey
Key ref: W.A.Macdonald et al. (2003). A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition. J Exp Med, 198, 679-691. PubMed id: 12939341
24-Oct-02     Release date:   16-Mar-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P30481  (1B44_HUMAN) -  HLA class I histocompatibility antigen, B-44 alpha chain
362 a.a.
276 a.a.*
Protein chain
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin
119 a.a.
99 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   15 terms 
  Biological process     immune system process   21 terms 
  Biochemical function     protein binding     3 terms  


J Exp Med 198:679-691 (2003)
PubMed id: 12939341  
A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition.
W.A.Macdonald, A.W.Purcell, N.A.Mifsud, L.K.Ely, D.S.Williams, L.Chang, J.J.Gorman, C.S.Clements, L.Kjer-Nielsen, D.M.Koelle, S.R.Burrows, B.D.Tait, R.Holdsworth, A.G.Brooks, G.O.Lovrecz, L.Lu, J.Rossjohn, J.McCluskey.
HLA-B*4402 and B*4403 are naturally occurring MHC class I alleles that are both found at a high frequency in all human populations, and yet they only differ by one residue on the alpha2 helix (B*4402 Asp156-->B*4403 Leu156). CTLs discriminate between HLA-B*4402 and B*4403, and these allotypes stimulate strong mutual allogeneic responses reflecting their known barrier to hemopoeitic stem cell transplantation. Although HLA-B*4402 and B*4403 share >95% of their peptide repertoire, B*4403 presents more unique peptides than B*4402, consistent with the stronger T cell alloreactivity observed toward B*4403 compared with B*4402. Crystal structures of B*4402 and B*4403 show how the polymorphism at position 156 is completely buried and yet alters both the peptide and the heavy chain conformation, relaxing ligand selection by B*4403 compared with B*4402. Thus, the polymorphism between HLA-B*4402 and B*4403 modifies both peptide repertoire and T cell recognition, and is reflected in the paradoxically powerful alloreactivity that occurs across this "minimal" mismatch. The findings suggest that these closely related class I genes are maintained in diverse human populations through their differential impact on the selection of peptide ligands and the T cell repertoire.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21301478 S.Gras, L.Kjer-Nielsen, Z.Chen, J.Rossjohn, and J.McCluskey (2011).
The structural bases of direct T-cell allorecognition: implications for T-cell-mediated transplant rejection.
  Immunol Cell Biol, 89, 388-395.  
20212169 A.Theodossis, C.Guillonneau, A.Welland, L.K.Ely, C.S.Clements, N.A.Williamson, A.I.Webb, J.A.Wilce, R.J.Mulder, M.A.Dunstone, P.C.Doherty, J.McCluskey, A.W.Purcell, S.J.Turner, and J.Rossjohn (2010).
Constraints within major histocompatibility complex class I restricted peptides: presentation and consequences for T-cell recognition.
  Proc Natl Acad Sci U S A, 107, 5534-5539.
PDB codes: 3l3d 3l3g 3l3h 3l3i 3l3j 3l3k
20657836 B.Knapp, U.Omasits, W.Schreiner, and M.M.Epstein (2010).
A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.
  PLoS One, 5, e11653.  
20131248 H.Fabian, H.Huser, B.Loll, A.Ziegler, D.Naumann, and B.Uchanska-Ziegler (2010).
HLA-B27 heavy chains distinguished by a micropolymorphism exhibit differential flexibility.
  Arthritis Rheum, 62, 978-987.  
21042237 N.A.Mifsud, T.H.Nguyen, B.D.Tait, and T.C.Kotsimbos (2010).
Quantitative and functional diversity of cross-reactive EBV-specific CD8+ T cells in a longitudinal study cohort of lung transplant recipients.
  Transplantation, 90, 1439-1449.  
20707881 N.E.Elamin, C.Bade-Doeding, R.Blasczyk, and B.Eiz-Vesper (2010).
Polymorphism between HLA-A*0301 and A*0302 located outside the pocket F alters the PΩ peptide motif.
  Tissue Antigens, 76, 487-490.  
20122941 N.G.Walpole, L.Kjer-Nielsen, L.Kostenko, J.McCluskey, A.G.Brooks, J.Rossjohn, and C.S.Clements (2010).
The structure and stability of the monomorphic HLA-G are influenced by the nature of the bound peptide.
  J Mol Biol, 397, 467-480.
PDB codes: 3kyn 3kyo
20566715 S.Gras, Z.Chen, J.J.Miles, Y.C.Liu, M.J.Bell, L.C.Sullivan, L.Kjer-Nielsen, R.M.Brennan, J.M.Burrows, M.A.Neller, R.Khanna, A.W.Purcell, A.G.Brooks, J.McCluskey, J.Rossjohn, and S.R.Burrows (2010).
Allelic polymorphism in the T cell receptor and its impact on immune responses.
  J Exp Med, 207, 1555-1567.
PDB codes: 3mv7 3mv8 3mv9
20536911 S.H.Hwang, H.B.Oh, S.E.Choi, J.J.Seo, J.H.Lee, S.W.Cho, J.M.Chae, Y.S.Heo, C.L.Chang, and E.Y.Lee (2010).
Impact of amino acid substitution at residue 9 of HLA-A2 on the development of acute GVHD in Korean pediatric patients receiving unrelated hematopoietic stem cell transplantation.
  Transpl Int, 23, 1216-1222.  
19317752 C.Figueiredo, S.Mbulaiteye, C.M.Ndugwa, T.Schulz, and B.Eiz-Vesper (2009).
Assessment of the amino acid substitution in HLA-B*5719 for allorecognition.
  Tissue Antigens, 73, 376-378.  
19139173 J.K.Archbold, W.A.Macdonald, S.Gras, L.K.Ely, J.J.Miles, M.J.Bell, R.M.Brennan, T.Beddoe, M.C.Wilce, C.S.Clements, A.W.Purcell, J.McCluskey, S.R.Burrows, and J.Rossjohn (2009).
Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition.
  J Exp Med, 206, 209-219.
PDB codes: 3dx6 3dx7 3dx8 3dx9 3dxa
18997170 T.Kawase, K.Matsuo, K.Kashiwase, H.Inoko, H.Saji, S.Ogawa, S.Kato, T.Sasazuki, Y.Kodera, and Y.Morishima (2009).
HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism.
  Blood, 113, 2851-2858.  
20064448 W.A.Macdonald, Z.Chen, S.Gras, J.K.Archbold, F.E.Tynan, C.S.Clements, M.Bharadwaj, L.Kjer-Nielsen, P.M.Saunders, M.C.Wilce, F.Crawford, B.Stadinsky, D.Jackson, A.G.Brooks, A.W.Purcell, J.W.Kappler, S.R.Burrows, J.Rossjohn, and J.McCluskey (2009).
T cell allorecognition via molecular mimicry.
  Immunity, 31, 897-908.
PDB codes: 3kpl 3kpm 3kpn 3kpo 3kpp 3kpq 3kpr 3kps
18243674 A.W.Purcell, and T.Elliott (2008).
Molecular machinations of the MHC-I peptide loading complex.
  Curr Opin Immunol, 20, 75-81.  
18004563 C.Wölfel, V.Lennerz, E.Lindemann, G.Hess, H.G.Derigs, C.Huber, W.Herr, and T.Wölfel (2008).
Dissection and molecular analysis of alloreactive CD8+ T cell responses in allogeneic haematopoietic stem cell transplantation.
  Cancer Immunol Immunother, 57, 849-857.  
18549801 D.Chessman, L.Kostenko, T.Lethborg, A.W.Purcell, N.A.Williamson, Z.Chen, L.Kjer-Nielsen, N.A.Mifsud, B.D.Tait, R.Holdsworth, C.A.Almeida, D.Nolan, W.A.Macdonald, J.K.Archbold, A.D.Kellerher, D.Marriott, S.Mallal, M.Bharadwaj, J.Rossjohn, and J.McCluskey (2008).
Human leukocyte antigen class I-restricted activation of CD8+ T cells provides the immunogenetic basis of a systemic drug hypersensitivity.
  Immunity, 28, 822-832.
PDB code: 2rfx
18342005 D.I.Godfrey, J.Rossjohn, and J.McCluskey (2008).
The fidelity, occasional promiscuity, and versatility of T cell receptor recognition.
  Immunity, 28, 304-314.  
18378495 J.K.Archbold, W.A.Macdonald, S.R.Burrows, J.Rossjohn, and J.McCluskey (2008).
T-cell allorecognition: a case of mistaken identity or déjà vu?
  Trends Immunol, 29, 220-226.  
18211710 J.Sidney, B.Peters, N.Frahm, C.Brander, and A.Sette (2008).
HLA class I supertypes: a revised and updated classification.
  BMC Immunol, 9, 1.  
18433045 K.J.Allen, N.A.Mifsud, R.Williamson, P.Bertolino, and W.Hardikar (2008).
Cell-mediated rejection results in allograft loss after liver cell transplantation.
  Liver Transpl, 14, 688-694.  
19047637 K.Kedzierska, C.Guillonneau, S.Gras, L.A.Hatton, R.Webby, A.W.Purcell, J.Rossjohn, P.C.Doherty, and S.J.Turner (2008).
Complete modification of TCR specificity and repertoire selection does not perturb a CD8+ T cell immunodominance hierarchy.
  Proc Natl Acad Sci U S A, 105, 19408-19413.
PDB code: 3cpl
18678247 L.K.Ely, S.R.Burrows, A.W.Purcell, J.Rossjohn, and J.McCluskey (2008).
T-cells behaving badly: structural insights into alloreactivity and autoimmunity.
  Curr Opin Immunol, 20, 575-580.  
18063114 L.Song, J.Le, F.Ye, H.Shao, H.J.Kaplan, and D.Sun (2008).
Sequence 168 to 177 of interphotoreceptor retinoid-binding protein (IRBP) is an antigenic epitope for autoreactive CD8 T cells in the B10RIII mouse.
  J Neuroimmunol, 193, 68-76.  
18991276 N.Hillen, G.Mester, C.Lemmel, A.O.Weinzierl, M.Müller, D.Wernet, J.Hennenlotter, A.Stenzl, H.G.Rammensee, and S.Stevanović (2008).
Essential differences in ligand presentation and T cell epitope recognition among HLA molecules of the HLA-B44 supertype.
  Eur J Immunol, 38, 2993-3003.  
18238896 N.L.La Gruta, P.G.Thomas, A.I.Webb, M.A.Dunstone, T.Cukalac, P.C.Doherty, A.W.Purcell, J.Rossjohn, and S.J.Turner (2008).
Epitope-specific TCRbeta repertoire diversity imparts no functional advantage on the CD8+ T cell response to cognate viral peptides.
  Proc Natl Acad Sci U S A, 105, 2034-2039.
PDB code: 3buy
18340360 R.D.Levinson, Z.Du, L.Luo, D.Monnet, T.Tabary, A.P.Brezin, L.Zhao, D.W.Gjertson, G.N.Holland, E.F.Reed, J.H.Cohen, and R.Rajalingam (2008).
Combination of KIR and HLA gene variants augments the risk of developing birdshot chorioretinopathy in HLA-A*29-positive individuals.
  Genes Immun, 9, 249-258.  
17473845 A.W.Purcell, J.McCluskey, and J.Rossjohn (2007).
More than one reason to rethink the use of peptides in vaccine design.
  Nat Rev Drug Discov, 6, 404-414.  
17242432 F.Sieker, S.Springer, and M.Zacharias (2007).
Comparative molecular dynamics analysis of tapasin-dependent and -independent MHC class I alleles.
  Protein Sci, 16, 299-308.  
17357107 J.M.Burrows, K.K.Wynn, F.E.Tynan, J.Archbold, J.J.Miles, M.J.Bell, R.M.Brennan, S.Walker, J.McCluskey, J.Rossjohn, R.Khanna, and S.R.Burrows (2007).
The impact of HLA-B micropolymorphism outside primary peptide anchor pockets on the CTL response to CMV.
  Eur J Immunol, 37, 946-953.  
17418777 J.Rossjohn, and J.McCluskey (2007).
How a home-grown T cell receptor interacts with a foreign landscape.
  Cell, 129, 19-20.  
18007679 N.J.Felix, and P.M.Allen (2007).
Specificity of T-cell alloreactivity.
  Nat Rev Immunol, 7, 942-953.  
17496542 S.Terakura, M.Murata, E.H.Warren, A.Sette, J.Sidney, T.Naoe, and S.R.Riddell (2007).
A single minor histocompatibility antigen encoded by UGT2B17 and presented by human leukocyte antigen-A*2902 and -B*4403.
  Transplantation, 83, 1242-1248.  
17011774 C.S.Clements, M.A.Dunstone, W.A.Macdonald, J.McCluskey, and J.Rossjohn (2006).
Specificity on a knife-edge: the alphabeta T cell receptor.
  Curr Opin Struct Biol, 16, 787-795.  
16091932 I.K.Egorov (2006).
Mouse models of efficient and inefficient anti-tumor immunity, with emphasis on minimal residual disease and tumor escape.
  Cancer Immunol Immunother, 55, 1.  
16451198 J.N.Torimiro, J.K.Carr, N.D.Wolfe, P.Karacki, M.P.Martin, X.Gao, U.Tamoufe, A.Thomas, E.M.Ngole, D.L.Birx, F.E.McCutchan, D.S.Burke, and M.Carrington (2006).
HLA class I diversity among rural rainforest inhabitants in Cameroon: identification of A*2612-B*4407 haplotype.
  Tissue Antigens, 67, 30-37.  
16761314 N.Auphan-Anezin, C.Mazza, A.Guimezanes, G.A.Barrett-Wilt, F.Montero-Julian, A.Roussel, D.F.Hunt, B.Malissen, and A.M.Schmitt-Verhulst (2006).
Distinct orientation of the alloreactive monoclonal CD8 T cell activation program by three different peptide/MHC complexes.
  Eur J Immunol, 36, 1856-1866.
PDB codes: 2clv 2clz
15592665 C.Bade-Doeding, B.Eiz-Vesper, C.Figueiredo, A.Seltsam, H.A.Elsner, and R.Blasczyk (2005).
Peptide-binding motif of HLA-A*6603.
  Immunogenetics, 56, 769-772.  
15718280 C.S.Clements, L.Kjer-Nielsen, L.Kostenko, H.L.Hoare, M.A.Dunstone, E.Moses, K.Freed, A.G.Brooks, J.Rossjohn, and J.McCluskey (2005).
Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the fetal-maternal interface.
  Proc Natl Acad Sci U S A, 102, 3360-3365.
PDB code: 1ydp
15896200 C.Vilches, S.Sepúlveda, A.Balas, R.Solís, M.J.Avilés, E.Estefanía, N.Gómez-Lozano, J.L.Vicario, and R.dePablo (2005).
Complete coding sequences and haplotypic associations of HLA-B*0707, -B*1524, -B*4405, -B*4802, -DRB1*0409, -DRB1*0411, -DRB1*1115, -DRB1*1305, and the novel allele -DRB1*0709. Group-specific amplification of cDNA from DRB1 alleles associated to DRB3 and DRB4.
  Tissue Antigens, 65, 529-538.  
16034430 D.I.Godfrey, J.McCluskey, and J.Rossjohn (2005).
CD1d antigen presentation: treats for NKT cells.
  Nat Immunol, 6, 754-756.  
16275762 F.E.Tynan, D.Elhassen, A.W.Purcell, J.M.Burrows, N.A.Borg, J.J.Miles, N.A.Williamson, K.J.Green, J.Tellam, L.Kjer-Nielsen, J.McCluskey, J.Rossjohn, and S.R.Burrows (2005).
The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation.
  J Exp Med, 202, 1249-1260.
PDB codes: 2axf 2axg
16186824 F.E.Tynan, S.R.Burrows, A.M.Buckle, C.S.Clements, N.A.Borg, J.J.Miles, T.Beddoe, J.C.Whisstock, M.C.Wilce, S.L.Silins, J.M.Burrows, L.Kjer-Nielsen, L.Kostenko, A.W.Purcell, J.McCluskey, and J.Rossjohn (2005).
T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I-bound peptide.
  Nat Immunol, 6, 1114-1122.
PDB code: 2ak4
15853897 J.M.Tiercy (2005).
Analysis of 250 HLA-B44 genotypes in European Caucasoids: high diversity and preferential ABCDRB1 associations in B*4402, B*4403, and B*4405 haplotypes.
  Tissue Antigens, 65, 429-436.  
16000083 N.A.Williamson, and A.W.Purcell (2005).
Use of proteomics to define targets of T-cell immunity.
  Expert Rev Proteomics, 2, 367-380.  
15871042 R.Sainudiin, W.S.Wong, K.Yogeeswaran, J.B.Nasrallah, Z.Yang, and R.Nielsen (2005).
Detecting site-specific physicochemical selective pressures: applications to the Class I HLA of the human major histocompatibility complex and the SRK of the plant sporophytic self-incompatibility system.
  J Mol Evol, 60, 315-326.  
16181329 T.Elliott, and A.Williams (2005).
The optimization of peptide cargo bound to MHC class I molecules by the peptide-loading complex.
  Immunol Rev, 207, 89-99.  
15226359 D.Zernich, A.W.Purcell, W.A.Macdonald, L.Kjer-Nielsen, L.K.Ely, N.Laham, T.Crockford, N.A.Mifsud, M.Bharadwaj, L.Chang, B.D.Tait, R.Holdsworth, A.G.Brooks, S.P.Bottomley, T.Beddoe, C.A.Peh, J.Rossjohn, and J.McCluskey (2004).
Natural HLA class I polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion.
  J Exp Med, 200, 13-24.
PDB codes: 1sys 1syv
14734527 M.Hülsmeyer, M.T.Fiorillo, F.Bettosini, R.Sorrentino, W.Saenger, A.Ziegler, and B.Uchanska-Ziegler (2004).
Dual, HLA-B27 subtype-dependent conformation of a self-peptide.
  J Exp Med, 199, 271-281.
PDB codes: 1of2 1ogt
15304005 R.Paris, S.Bejrachandra, C.Karnasuta, D.Chandanayingyong, W.Kunachiwa, N.Leetrakool, S.Prakalapakorn, P.Thongcharoen, S.Nittayaphan, P.Pitisuttithum, V.Suriyanon, S.Gurunathan, J.G.McNeil, A.E.Brown, D.L.Birx, and Souza (2004).
HLA class I serotypes and cytotoxic T-lymphocyte responses among human immunodeficiency virus-1-uninfected Thai volunteers immunized with ALVAC-HIV in combination with monomeric gp120 or oligomeric gp160 protein boosting.
  Tissue Antigens, 64, 251-256.  
15469407 S.H.Shoshan, and A.Admon (2004).
MHC-bound antigens and proteomics for novel target discovery.
  Pharmacogenomics, 5, 845-859.  
15304014 V.Mas, M.T.Arias, V.Fabregat, B.Nomdedeu, C.Serrapagès, J.Vives, J.Martorell, E.Carreras, and M.G.Ercilla (2004).
Description of a novel HLA-DRB1 allele found in a candidate for bone marrow transplantation.
  Tissue Antigens, 64, 304-307.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.