Immunological Self, Nonself Discrimination

Abstract

The ability of immunodominant peptides derived from several antigen systems to compete with each other for T cell activation was studied. Only peptides restricted by a given transplantation antigen are mutually competitive. There is a correlation between haplotype restriction, ability to bind to the appropriate transplantation antigen, and ability to inhibit activation of other T cells restricted by the same transplantation antigen. An exception was noted in that a peptide derived from an antigen, bacteriophage lambda cI repressor, binds to the I-Ed molecule in a specific way, yet is not I-Ed-restricted. Comparison of the sequence of the repressor peptide with that of other peptides able to bind to (and be restricted by) I-Ed and a polymorphic region of the I-Ed molecule itself revealed a significant degree of homology. Thus, peptides restricted by a given class II molecule appear to be homologous to a portion of the class II molecule itself. The repressor-derived peptide is identical at several polymorphic residues at this site, and this may account for the failure of I-Ed to act as a restriction element. Comparison of antigenic peptide sequences with transplantation antigen sequences suggests a model that provides a basis for explaining self, nonself discrimination as well as alloreactivity.

Creation of H-2 class I epitopes using synthetic peptides: recognition by alloreactive cytotoxic T lymphocytes.

“…Class II molecules have clearly been shown to present "processed" antigen or synthetic peptides to helper T cells (3)(4)(5). In contrast, only recently has work from several laboratories indicated that class I molecules may also bind synthetic peptides, thereby forming target structures that can be recognized by CTLs.…”

Mecanismos de procesamiento y presentación de antígeno en el sistema inmune

“…Debe haber por lo tanto un reconocimiento preferencial de ciertas secuencias de péptidos. En efecto, los primeros resultados muestras que hay tres tipos de estructuras (no excluyentes entre ellas) que pueden estar a la base de este reconocimiento selectivo: 1) péptidos amfifíli-cos que tendrían una parte hidrófoba, que haría contacto con el CMH, y una parte hidrofílica hacia el exterior, que haría contacto con el TCR; 2) aminoáci-dos cargados positivamente o glicinas, seguidos de 2 residuos hidrófobos y después un residuo polar o una glicina, y 3) péptidos que presentarían una homología con los antígenos del CMH (25,26).…”

De l’immunologie fondamentale au développement de la vaccinologie

“…< Cet article est dédié à la mémoire de Jean-Gérard Guillet [4]. Ces constatations ont conduit à proposer un modèle : dans la cellule présentatrice, les peptides issus de tous les antigènes dégradés se fixent sur un même site de la molécule du CMH, et la présence de ce site polymorphique, assurant la liaison de peptides très variés, peut expliquer la sélection du soi dans le thymus et la restriction par le CMH [5]. Peu après, l'association physique entre divers peptides immunogènes et les molécules de classe I du CMH humain, le système HLA, a été démontrée dans l'U152 Inserm de Jean-Paul Lévy à l'hôpital Cochin [6,7].…”