T-cell receptor usage in alloreactivity against HLA-B*2703 reveals significant conservation of the antigenic structure of B*2705.
B*2703 is an exceptional HLA-B27 molecule in that it differs from the most common B*2705 subtype by a unique amino acid change (His59) altering N-terminal peptide anchorage. To assess how this unusual feature affects the antigenic structure of HLA-B27, TCR usage by alloreactive CTL raised against B*2703 from two individuals was analyzed. Only few CTL recognized B*2703 from two individuals was analyzed. Only few CTL recognized B*2703 but nor ot at a lower level B*2705. Limited heterogeneity of these CTL was revealed by: 1) identity of TCR in two pairs of such CTL clones, 2) identity of beta chains, paired to distinct alpha chains, in two clonotypes, and 3) almost identical fine specificity of these two clonotypes with site-specific HLA-B27 mutants. These results indicate that B*2703 "private" epitopes are rare. TCR usage among anti-B*2703 CTL was analogous as in anti-B*2705 responses in the predominant and donor-independent usage of V beta segments from homology subgroup 4, more moderate and donor-dependent V alpha skewing, N+D beta diversity limited by motifs shared among clonotypes, and restricted J alpha heterogeneity. Homology of N+D beta motifs and J alpha segments of anti-B*2703 with anti-B*2705 TCR suggested significant sharing of peptide-associated epitopes between both subtypes. The results indicate that allospecific TCR are recruited by B*2703 following similar rules as in the anti-B*2705 response, and suggest that the B*2703 change keeps unaltered much of the antigenic structure of the molecule relative to B*2705. Therefore, most of the peptides bound to B*2703 should be the same and keep a similar conformation as in B*2705.
Barber
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DF
Centro de Biología Molecular Severo Ochoa, (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Facultad de Clencias, Madrid, Spain.
Obeso
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D
Carcía-Hoyo
R
R
Villadangos
J A
JA
López de Castro
J A
JA
D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta