Recognition of distinct epitopes on the HLA-A2 antigen by cytotoxic T lymphocytes》.pdf

Recognition of Distinct Epitopes on the HLA- A2 Antigen by Cytotoxic T Lymphocytes Jan J. van der Poel, Jos Pool, Els Goulmy, Marius J. Giphart, and Jon J. van Rood A B S T R A C T : Alloimmune CTLs specifically recognizing the HLA-A2.3 subtype could be made besides the previously described HLA-A2,1 and A2.2 subtype-specific CTLs. Examination of thefine specificity of 15 different CTLs directed against distinct HLA-A2 subtypes demonstratedfurther complexity of antigenic epitopes present on the A2 molecule. First, epitopes could be defined which are unique for the HLA-A2.1, A2.2, A2.3, and A2.4 subtypes. Second, epitopes could be defined which are shared between the HLA-A2.1, A2.2 and A2.4 subtypes, but which are not shared by the A2.3 subtype. Analysis of the reactivity patterns of CTLs directed against the HLA-A2.2 and A2.4 subtypes indicated that the observed cytotoxic response was dependent on the HLA type of the responder cell. Biochemical analysis demonstrated the existence of isoelectricpoint variation in A2 heavy chains which deviated from the expected pls for the A2 subtypes as described previously. Individuals were identified whopossessedA2 heavy chains typicalfor the A2.3 subtype antigen although the CTL analysis demonstrated the presence of an A2.1 subtype antigen. ABBREVIATIONS CML cell mediated lympholysis MoAb monoclonal antibody CTL cytotoxic T lymphocyte MHC major histocompatibility IEF isoelectric focusing complex RCR relative cytotoxic response