THE ROLE OF THE CONSERVED RESIDUE IN POCKET-A AND THE POLYMORPHIC RESIDUE IN POCKET-E OF HLA-B(ASTERISK)3501 IN PRESENTATION OF HUMAN MINORHISTOCOMPATIBILITY PEPTIDES TO T-CELLS

We investigated T cell recognition for human minor histocompatibility (hmH) peptides using HLA-B3501 restricted, hmH specific cytotoxic T l ymphocytes (CTL) clones. These CTL clones killed C1R cells expressing HLA-B3501 but not C1R cells expressing chimeric antigens between HLA- B3501 and HLA-B*5101. They also failed to kill C1R cells expressing H LA-B3501 mutants at residue 152 (B*3501-V152E) or at residue 171 (B*3 501-Y171H). The CTL clone failed to kill C1R cells expressing these mu tant molecules loaded with the hmH peptides isolated from C1R-B3501 c ells although it killed a self-B cell line expressing HLA-B3501 loaded with the specific hmH peptides. The CTL clone also failed to kill T2 cells expressing the mutant molecules loaded with the specific peptide s whereas it killed T2 cells expressing HLA-B3501 loaded with the spe cific peptide. On the other hand, naturally occurring specific hmH pep tides were isolated from purified B3501-V152E and B*3501-Y171H molecu les, indicating that both HLA-B3501-V152E and HLA-B*3501-Y171H molecu les can bind the hmH peptides. These findings indicate that both the c onserved residue 171 in pocket A and the polymorphic residue 152 in po cket E are critical in recognition of the T cells but not binding of t he hmH peptides. Furthermore, these results provide the possibility th at the TCR recognizes a conformational structure of hmH peptides bound to HLA-B3501 molecules.