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Differences in the recognition by CTL of peptides presented by the HLA-B*4402 and the HLA-B*4403 molecules which differ by a single amino acid

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Herman, Jacques [UCL] Jongeneel, V Kuznetsov, D Coulie, Pierre G. [UCL]

The HLA-B*4402 and B*4403 molecules differ only at residue 156, which borders the peptide binding site. Strong in vivo allogeneic reactions mediated by cytolytic T lymphocytes (CTLs) were reported in patients who received a bone marrow graft mismatched fur these B44 subtypes, indicating that HLA-B*4402 and B*4403 molecules present distinct antigens. This could be due either to the presentation of different sets of antigenic peptides or to the recognition by CTLs of conformational epitopes formed by the MHC molecules alone or in association with antigenic peptides. To address this question, we compared the two B44 sublypes in their presentation to tumor-specific CTLs of three peptides, encoded by genes MAGE-3, MUM-1 and Tyrosinase. The peptides bound with similar affinities to B*4402 or B*4403 molecules, as assessed by lytic competition assays. One HLA-B*4402-restricted and one HLA-B*4403-restricted CTL clone were derived against each peptide. When tested for lysis of B*4402 and B*4403 cells incubated with the antigenic peptides, most CTLs showed a marked preference for one of the two B44 subtypes Using variant peptides incorporating single alanine substitutions, we compared a given CTLs' recognition of its antigenic peptide presented by both B44 subtypes. Some substitutions, which had no effect on the binding of the peptide, affected its recognition by the same CTL differently on B*4402 and B*4403 molecules. These results imply that the conformations adopted by the same peptide on the two HLA-B44 subtypes are different, me conclude that the B44 subtype specificity of T cells results mostly from distinct conformations adopted by the same peptides in the two B44 molecules, This does trot exclude the possibility that in some cases the B44 subtype specificity results from the selective binding of a peptide to one subtype. We found several peptides, different from the three mentioned above, that contain the canonical HLA-B44 binding motif and bind to B*4403 but not to B*4402 molecules.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 1999
Language Anglais
Journal information "Tissue Antigens" - Vol. 53, no. 2, p. 111-121 (1999)
Peer reviewed yes
Publisher Munksgaard Int Publ Ltd (Copenhagen)
issn 0001-2815
Publication status Publié
Affiliations UCL - ESPO/POLS - Département des sciences politiques et sociales
UCL - MD/BICL - Département de biochimie et de biologie cellulaire
Keywords antigen ; CTL ; MHC ; peptide
Links
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Bibliographic reference Herman, Jacques ; Jongeneel, V ; Kuznetsov, D ; Coulie, Pierre G.. Differences in the recognition by CTL of peptides presented by the HLA-B*4402 and the HLA-B*4403 molecules which differ by a single amino acid. In: Tissue Antigens, Vol. 53, no. 2, p. 111-121 (1999)
Permanent URL http://hdl.handle.net/2078.1/44587