T-lymphocyte recognition of sperm-whale myoglobin. Responses of T-cells from mouse strains primed with synthetic peptide carrying antigenic site 5 and relation to antigen presentation.

Abstract

SUMMARYIn the preceding communication of this series, the fine specificity requirements for T‐cell recognition of one of the Mb antigenic sites (antigenic site 5) were examined. Seven synthetic peptides containing antigenic site 5 and progressively increasing in length to the left by increments of two residues up to 22 residues in length were studied with regard to their ability to stimulate T‐cell proliferation of Mb‐primed T‐cells from high responder H‐2d and H‐2s mouse strains. Unexpectedly, it was found that, unlike smaller and longer peptides, some intermediate‐sized peptides failed to stimulate T‐cell proliferation even though they contained the full antigenic site. This indicated that lack of proliferative stimulating activity by a peptide does not necessarily imply absence of an antigenic site in the peptide. The results enabled us to conclude that T‐cell recognition of native proteins (or at least of Mb) is dependent on protein conformation. In the present work, we have examined the ability of peptide‐primed T‐cells from H‐2d and H‐2s mouse strains to proliferate to Mb. Immunization with peptide 145‐151 (antigenic site 5) afforded T‐cells that did not proliferate in vitro to Mb or any of the synthetic peptides 145‐153, 143‐153, 141‐153, 139‐153, 137‐153, 135‐153 or 132‐153. When mice were primed with either peptide 143‐153 (11 residues) or peptide 132‐153 (22 residues), The T‐cells obtained did not respond to Mb but responded in each case very well to peptides 132‐153, 135‐153, 137‐153 and gave lower, but significant, response to the shorter peptides 145‐153 and 143‐153. Intermediate‐sized peptides did not stimulate T‐cell proliferations and neither did truncated peptides that had deletions at Tyr‐151 and Ala‐144. These findings underscore the fine specificity of the T‐cell and indicate a high level of conformational dependency for T‐cell recognition. It is also concluded that macrophage recognition and presentation of protein antigen must involve the intact native protein and it is probably not related to the processing and fragmenting of the antigen by macrophage. The latter activity is more related to the role of macrophage in clearance.