H—2-restricted cytolytic T cells specific for HLA can recognize a synthetic HLA peptide

Abstract

It is generally accepted that T lymphocytes recognize antigens in the context of molecules encoded by genes in the major histocompatibility complex (MHC). MHC class II-restricted T cells usually recognize degraded or denatured rather than native forms of antigen on the surface of class II-bearing antigen presenting cells. It has recently been shown that short synthetic peptides corresponding to mapped antigenic sites of the influenza nucleoprotein (NP) can render uninfected target cells susceptible to lysis by NP-specific class I-restricted cytolytic T cells (CTL). These and earlier experiments that showed specific recognition of NP deletion mutant transfectants suggest that class I-restricted recognition might also involve processed antigenic fragments. One important issue arising from these studies is whether the model applies not only to viral proteins that are expressed internally (such as NP) but also to antigens normally expressed as integral membrane proteins at the cell surface. We have recently isolated class I-restricted mouse CTL clones that recognize class I gene products of the human MHC (HLA) as antigens in mouse cell HLA-transfectants. Here we show that these anti-HLA CTL can lyse HLA-negative syngeneic mouse cells in the presence of a synthetic HLA peptide. These results suggest that the model applies generally.

Characterization of mixed syngeneic-allogeneic and syngeneic-xenogeneic islet-graft rejections in mice. Evidence of functional impairment of the remaining syngeneic islets in xenograft rejections.

“…plantation, a pronounced first peak of insulin release in re-This notion is further supported by the identification ofspecific sponse to a glucose stimulus was observed from the syngeneic oligopeptides ofxenogeneic MHC class I antigen in association grafts in group A. This was followed by a slightly smaller secwith recipient MHC molecules (21,22). However, this comond phase of insulin release, which promptly returned to basal bined antigen (xenopeptide and recipient MHC) is not present levels when the glucose stimulus was removed (Fig.…”

Cellular Immune Recognition and the Biological Role of Major Transplantation Antigens

“…He showed that class I molecules of virus-infected cells present peptides, 9-10 amino acids in length, to virus-specific cytotoxic T-cells. Similar results were obtained by J. Maryanski and coworkers [64]. These peptides became very real when they were first eluted from target cells by the group of H. G. Rammensee [65].…”

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

“…In addition, influenza hemagglutinin-specific CTLs can recognize the transmembrane sequence ofhemagglutinin in the context ofthe Kd molecule (7). Maryanski et al have shown that cloned CTLs can recognize a human class I peptide in the context of the H-2Kd molecule (8), while certain cloned HLA-A2-specific alloreactive CTLs have been shown to recognize a complex ofan A2 peptide and the Aw69 molecule (9). The class I-derived peptide Ld61-85, together with the Dk molecule, has also been shown to be recognized by certain Ld-specific CTL clones (10).…”