Immunological focusing by the mouse major histocompatibility complex: Mouse strains confronted with distantly related lysozymes confine their attention to very few epitopes

Abstract

The gallinaceous lysozymes are a family of antigens that are distantly related to mouse lysozyme. A T cell-dependent proliferation assay was used to characterize the spectrum of reactivities to lysozyme determinants in B10-congenic mice. Cross-reactivity studies, using a panel of species variant lysozymes to stimulate lymph node cells from chicken egg white lysozyme- and ring-necked pheasant egg white lysozyme-primed B10.D2 mice, indicated a preferential focusing of T cell reactivity onto a single determinant containing amino acids 113-114. The data, in conjunction with results obtained by priming with cyanogen bromide cleavage fragments of lysozymes, suggested that a site common to the L3 region (amino acids 106-129) of all the lysozymes tested was a preferential anchorage site for I region-encoded Ia molecules on H-2d antigen-presenting cells; this leads to the limited display of a determinant containing residues 113-114. Priming with L2H (amino acids 13-105), a peptide containing the major epitopes recognized by B10.A and B10 mice, failed to stimulate any T cell proliferation by B10.D2 lymph node cells. The Ia molecules in any one mouse strain apparently attach to very few sites on lysozyme to effectively display antigenic determinants for T cell activation. This result points to a model of limited determinant selection even on a very foreign antigen, based upon a shortage of appropriate amino acid residues usable by Ia antigen-presenting structures of a strain.