A human CTL recognizes a caspase-8-derived peptide on autologous HLA-B*3503 molecules and two unrelated peptides on allogeneic HLA-B*3501 molecules.
A CTL clone that recognizes autologous tumor cells was previously isolated from the blood of a head-and-neck cancer patient. The Ag was identified as peptide FPSDSWCYF presented by autologous HLA-B*3503 molecules. This peptide was encoded by a mutated CASP-8 gene, which is implicated in the triggering of apoptosis. Here, we show that this CTL clone, which expresses a single TCR, also recognizes two unrelated peptides on allogeneic HLA-B*3501 molecules. One peptide, HIPDVITY, is encoded by squalene synthase, and the other one, QFADVIVLF, is encoded by 2-hydroxyphytanoyl-CoA lyase. Both genes are expressed ubiquitously. These antigenic peptides are processed and presented by HLA-B*3501 cells. The two HLA-B35 alleles are closely related. Our results might reinforce the notion that the recognition of allogeneic HLA molecules depends on the presence in their groove of a limited number of peptides processed from ubiquitous proteins.
Mandruzzato
S
S
Ludwig Institute for Cancer Research, Brussels Branch, and Unité de Génétique Cellulaire, Université Catholique de Louvain, Brussels, Belgium.
Stroobant
V
V
Demotte
N
N
van der Bruggen
P
P
D000368:Aged; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D019556:COS Cells; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D018076:DNA, Complementary / Q000032:analysis; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000235:genetics; D005260:Female; D015797:HLA-B35 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D015797:HLA-B35 Antigen; D009842:Oligopeptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013186:Farnesyl-Diphosphate Farnesyltransferase; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases