T cell response to myoglobin: a comparison of T cell clones in high‐responder and low‐responder mice

Abstract

Mice carrying the H-2b haplotype (e.g., inbred strains C57BL/6 and C57BL/10) are low responders to sperm whale myoglobin when tested in the T cell proliferation assay. Their response is improved by the removal of the Ly-2+ cells from the lymph node population, but it still remains significantly lower than that of cells cells from high-responder strains (e.g., DBA/2, H-2d). To determine whether T cells from the low and high-responder mice recognize the same or different epitopes on the immunizing antigen, we obtained sets of T cell clones from both strains and tested them against peptides representing different regions of the myoglobin molecule, as well as against myoglobins from species other than the sperm whale. Four types of T cell clones were obtained from the DBA/2 mice: 3 types responded to the peptide 107-120 (9 clones altogether), and 1 type responded to the peptide 133-149 (4 clones altogether). The 3 types responding to the peptide 107-120 could be distinguished by their response to horse myoglobin or by the restriction of the response (Ad vs. Ed). Similarly, 5 types of T cell clones were obtained from the C57BL/6 mice: 2 types responded to the peptide 10-22 (1 type, but not the other, responded to horse myoglobin); 1 type responded to the peptide 133-149; and 2 types did not respond to any of the peptides used (1 type, but not the other, responded to dog myoglobin). All 5 types (13 clones altogether) were presumably Ab restricted. These results demonstrate the diversity of epitopes in single antigenic regions and show equivalent heterogeneity of T cell repertoires in high and low responder mice. Attempts to demonstrate specific T cell suppression in the low responder mice failed; only partial, nonspecific suppression was observed.

Antigen processing by endosomal proteases determines which sites of sperm‐whale myoglobin are eventually recognized by T cells

“…only the residues C terminal from the cleavage site. This is exemplified by our finding that the fragment 15-29 contains a Tcell epitope (see below), presumably the one previously located between residues 13 and 22 [30,33]. The correspondence between myoglobin T cell epitopes and the predominant degradation products as identified here is illustrated in Fig.…”

“…One is located between residues 70 and 78 [2,30] and thus, is fully comprised by the fragment 70-100. Two other minor epitopes, of which the exact boundaries have not yet been determined, are located between residues 13 and 22 [30,33] and between residues T-cell epitopes 26 and 40 [36]. A large part of these sequences coincides with those of the cathepsin D-released fragments 15-29 and 33-69, respectively.…”

Mapping of the full profile of T cell allorecognition regions on HLA‐DR2β subunit

“…T cell lines were, therefore, prepared in which the population of the DR2-specific alloreactive T cells was enriched by repeated stimulation in vitro with three alternating B cell lines bearing DR2 but expressing different HLA backgrounds. It should be noted that the preparation of both T cell lines and Tcell clones can lead to distortions [ 19,27,28] of theT cell repertoire relative to the in vivo situation. The distortions are usually more pronounced with cloning.…”

“…The cell surface protein HLA-DR, which is the most abundant of the human class I1 histocompatibility proteins, is composed of a (33)(34)(35) and P (27)(28)(29) subunits [l]. One or two DRP chains may be expressed, depending on the haplotype [2, 31.…”

Human immunodeficiency virus type‐1‐specific immune responses induced by DNA vaccination are greatly enhanced by mannan‐coated diC14‐amidine

“…injected every 2 days. Seven days after the last vaccination, 10 pg IIIB V3 peptide or myoglobin peptide [20] were injected into mouse footpads. After 24 h, the extent of footpad swelling was estimated as the difference in thickness between the pre-and post-injected footpads in units of lo-* mm.…”