T-CELL RECEPTOR USAGE IN ALLOREACTIVITY AGAINST HLA-B-ASTERISK-2703 REVEALS SIGNIFICANT CONSERVATION OF THE ANTIGENIC STRUCTURE OF B-ASTERISK-2705

B2703 is an exceptional HLA-B27 molecule in that it differs from the most common B2705 subtype by a unique amino acid change (His59) alter ing N-terminal peptide anchorage. To assess how this unusual feature a ffects the antigenic structure of HLA-B27, TCR usage by alloreactive C TL raised against B2703 from two individuals was analyzed. Only few C TL recognized B2703 but not or at a lower level B*2705. Limited heter ogeneity 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 a chains, in two clonotypes, and 3) almost identical fine specificity of these two clonotypes with site-specific HLA-B27 mutants. These result s indicate that B2703 ''private'' epitopes are rare. TCR usage among anti-B2703 CTL was analogous as in anti-B*2705 responses in the predo minant and donor-independent usage of V beta segments from homology su bgroup 4, more moderate and donor-dependent Va skewing, N+D beta diver sity limited by motifs shared among clonotypes, and restricted J alpha heterogeneity. Homology of N+D beta motifs and J alpha segments of an ti-B2703 with anti-B*2705 TCR suggested significant sharing of peptid e-associated epitopes between both subtypes. The results indicate that allospecific TCR are recruited by B2703 following similar rules as i n the anti-B2705 response, and suggest that the B*2703 change keeps u naltered much of the antigenic structure of the molecule relative to B 2705. Therefore, most of the peptides bound to B*2703 should be the s ame and keep a similar conformation as in B2705.