IR Gene Control as a Consequence of Holes in the Antigen Specific Repertoire of T lymphocytes

Abstract

To determine the site of the Ir gene defects in T cell responses we have employed a variety of small synthetic peptide antigens. It was thought that by precisely identifying the antigenic determinants involved in T cell recognition, it would be possible to assign the primary defect to either T cells or the stimulating macrophages. Using this approach we have tested over fifty peptides for immunogenicity and antigenicity in strain 2 and strain 13 guinea pigs and found that for any one antigen there was only around a 25% probability that any one guinea pig strain would produce an immune response; most peptides were nonantigenic and nonimmunogenic (1,2). We also noticed that those peptides that were immunogenic for strain 2 animals were rarely immunogenic for strain 13 guinea pigs, and vice versa. Since these two guinea pig strains differ only with respect to the Ia antigens of the MHC, it was clear that these patterns of responsiveness seemed to be associated with Ia antigens. Moreover, using very closely related peptide homologues containing single residue substitutions, we found no clearcut distinctions between the specificity of T cell responsiveness and Ir gene control.