The HLA-A2 and -A3 genes were used to construct intra-exon hybrids in which part of the third exon (corresponding to the second domain) was of one type and the rest of the other. Murine P815 cells expressing these hybrid constructs were assayed with human alloreactive cytotoxic T-lymphocyte lines specific for either HLA-A2 or HLA-A3. Specific recognition patterns were obtained which indicate that, in some cases, a small portion of the HLA-A2 sequence in an HLA-A3 background is sufficient for recognition by HLA-A2-specific cytotoxic T cells.

Cell Line↗

PubMedDate not supplied

Study of the immunogenicity of different recombinant Mengo viruses expressing HIV1 and SIV epitopes.

Recombinant Mengo viruses expressing heterologous genes have proven to be safe and immunogenic in both mice and primates, and to be able to induce both humoral and cellular immune responses (Altmeyer et al., 1995, 1996). Several recombinant Mengo viruses expressing either a large region (aa 65-206) of the HIV1 nef gene product, or cytotoxic T lymphocyte (CTL) epitopic regions from the SIV Gag (aa 182-190), Nef (aa 155-178) and Pol (aa 587-601) gene products were engineered. The heterologous antigens were expressed either as fusion proteins with the Mengo virus leader (L) protein, or in cleaved form through autocatalytic cleavage by the foot-and-mouth disease virus 2A protein. Rhesus macaques and BALB/c mice inoculated with the Mengo virus SIV recombinants failed to develop CTL responses against the SIV gene products, while one of the HIV-Nef recombinants induced a weak CTL response in mice directed to an HIV1 Nef peptide spanning positions 182-198. In contrast, BALB/c mice immunized with vaccinia virus recombinants expressing HIV1 Nef developed a strong CTL response to the 182-198 peptide and also responded to a second peptide spanning positions 73-81. These results indicate that Mengo virus recombinants expressing HIV1 Nef and SIV CTL epitopes are weak immunogens. One of the fusion recombinants expressing SIV CTL epitopes failed to infect macaques even when used at high doses, while the recombinant expressing HIV1 Nef as a fusion protein failed to infect BALB/c mice. These results demonstrate that the expression of certain heterologous sequences as fusion proteins with L can result in the loss of the ability of the recombinant to infect normally susceptible animals.

Amino Acid Sequence↗

PubMedDate not supplied

Murine cells expressing an HLA molecule are specifically lysed by HLA-restricted antiviral human T cells.

Class I HLA (histocompatibility locus antigen) molecules are the targets of allospecific cytolytic T lymphocytes (CTL) in graft rejection, and constitute the restricting elements necessary for the interaction between antiviral CTL and virus-infected cells. Cells expressing only one HLA in the absence of other human molecules would provide a remarkable model for studying the function of these molecules. However, HLA+ murine cells transfected with human genes are generally not lysed by allospecific human CTL, and this is ascribed to insufficient HLA expression, lack of human beta 2-microglobulin, alteration of HLA molecules or absence of receptors for human T8 or LFA1 molecules in murine cells. Here we report, for the first time, the specific lysis of virus-infected HLA+ murine cells by HLA-restricted antiviral human CTL. Therefore, these murine cells constitute an excellent model for studying the role of HLA molecules.

Animals↗

PubMedDate not supplied

[Role of H-2 region in cytolysis of viral induced lymphomas by T lymphocytes].

The cytolyse of lymphoma cells by anti-MSV-CTL requires an H-2 identity on CTL and target cells. It can be limited to D or K antigens. An altered cells hypothesis is the more likely hypothesis in H-2a or H-2d tumour cells. However the D antigen alone is involved in H-2b tumours Arguments are given which supports the existence of Ir genes controlling the formation of CTL against H-2Dd modified by MSV.

Animals↗