The identification of tyrosine as a common key residue in unrelated H-2Kd restricted antigenic peptides

we have compared the activity of several Kd-or Ld-restricted antigenic peptides as competitors in a functional competition assay using cytolytic T lymphocyte (CTL) clones. All of four unrelated Kd-restricted peptides tested could compete with each other but not with the Ld-restricted peptide P91A-.12-24 (P91A). Moreover, the P91A peptide falled to compete with the four Kd-restricted peptides. In contrast, another Ld-restricted peptide[mouse cytomegalovirus (MCMV) pp89 167-176] could clearly compete with both Kd- and Ld-restricted peptides. The comparison of a series of modified MCMV pp89 peptides suggested that distinct structural features allow the Interaction of the peptide with the two different MHC class I molecules. We showed previously that the competitor activity of two different Kd-restricted antigenic peptides was reduced substantially upon Ala substitution of the single Tyr residues present in these peptides. We now show a similar effect for two additional Kd-restricted peptides. Our results thus suggest that Tyr may function as an ‘anchor' residue for many antigentic peptides that bind to the Kdmolecule. Molecular modeling of the presumed antigen-binding site of the Kdmolecule revealed the presence of two deep cavities that may be involved in binding peptide amino acid side chains. A model Illustrating one possible interaction of a Tyr-containing peptide with the Kdmolecule is presente

Etude génétique comparée des systèmes de restriction et modification de l'ADN d'Escherichia coli et de Salmonella typhimurium

dissertn: Diss. Doct

Defined antigens recognized by T lymphocytes on human tumors.

Several independent groups have developed methods aimed at identifying antigens that are expressed on human tumors and can be recognized by T lymphocytes. The positively identified antigens can be presently classified as follows: 1) antigens derived from genes whose functions are still unknown that are expressed in significant proportions of tumors of various histologic types but not expressed in most normal tissues, 2) differentiation antigens expressed in melanomas, 3) mucins, 4) viral antigens, and 5) products of abnormal genes expressed in tumors. These results are presented with explanations about the methodologies used to identify these antigens in the perspective of their use in immunotherapy

Identification of a novel HLA-Cw*05 allele, Cw*0503

HLA-Cw*05 is one of the least polymorphic subgroups of HLA-C; so far only two alleles, namely Cw*0501 and Cw*0502, have been reported. We report here the identification of a third allele, Cw*0503, in a Caucasian individual. Cw*0503 is closely related to Cw*0501 with only six nucleotide substitutions clustering over a fragment of 48 nucleotides at the beginning of exon 4. All these six substitutions at the same positions have been found only in HLA-B*44 alleles, suggesting that Cw*0503 is a result of recombination between Cw*0501 and one of B*44 alleles

Tum- Mutation P35b Generates the Mhc-binding Site of a New Antigenic Peptide

Immunogenic tumor cell variant P35 was obtained by mutagen treatment of mouse mastocytoma P815. It expresses a potent new antigen recognized by syngeneic cytolytic T lymphocytes (CTL). This antigen is the result of a point mutation in a gene that is expressed by most healthy cells. A decapeptide encoded by the region spanning the mutation sensitized P815 cells to the relevant CTL, whereas the homologous decapeptide corresponding to the normal sequence did not. Only die mutant decapeptide was capable of enhancing the expression of the D(d)-presenting molecule at the cell surface, indicating that the mutation generates a motif which enables the antigenic peptide to bind to D(d)