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M Brenan

Publications and source records attributed to M Brenan.

26 records · Page 2Linked to original sources
PubMed1982

Non-H-2 and H-2-linked immune response genes control the cytotoxic T-cell response to H-Y.

The immunoregulation of cytotoxic T-cell responses to the male-specific antigen H-Y in mice has been found to be genetically controlled by genes of the major histocompatibility complex (H-2). Responsiveness was mainly confined to H-2b strains, but it has also been found in recombinant strains, F1 hybrids, and chimeras that carry at least part of the H-2b haplotype. By using a different immunization procedure it has been shown recently that an H-2k mouse strain (CBA) is also able to mount an equivalent H-Y-specific response. We investigate here, by applying this immunization technique, the responsiveness of other H-2k strains and of strains of other independent H-2 haplotypes. Both responders and nonresponders are found in three haplotypes: k, s, and d. The strain distribution pattern of responsiveness shows a combined influence of non-H-2 and H-2 genes. In certain strains there is a high variability in responsiveness between genetically identical individual animals. We discuss a model of immune response (Ir) gene function which could account for these observations.

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PubMed1982

H-2-associated differences in replicated strains of mice divergently selected for body weight.

A random-bred strain (Q) was established and divided into six replicates. Each replicate was divergently selected for 6-week weight (for over 30 generations) and each had an unselected control. We have investigated the H-2 haplotype of individual mice of the 18 selected Q strains to determine whether selection for size had also selected for H-2 or H-2-linked genes. From the results it appeared that only the H2b and H-2q haplotypes were present in the foundation stock. A large number of individuals of the six small sublines were of H-2b haplotype, while the majority of those of the six large sublines were of the H-2q haplotype. Individuals in the six control strains were H-2b, H-2q or both (i.e., H-2 heterozygotes and/or H-2 recombinants). These results suggest that control of body size is associated with H-2 or an H-2-linked gene(s).

Animals↗
PubMed1981

Analysis of H-2 determinants recognized during the induction of H-Y-immune cytotoxic T cells by monoclonal antibodies in vitro.

Monoclonal antibodies directed to the D region of H-2(k) when present during in vitro culture inhibit the generation of CBA/H and C3H.H-2(o) H-Y-immune cytotoxic T cells . Monoclonal antibodies directed to the I-A(k) and I-E(k) region specifically inhibited induction of CBA/H H-Y-immune cytotoxic T cells only when they were present simultaneously in culture. These findings show T helper cell requirement for CBA/H H-Y-immune cytotoxic T cell induction, and suggest that two I region-coded restriction antigens for T helper cells are involved.

Animals↗
PubMed1981

Analysis of haplotype preference in the cytotoxic T-cell response to H-Y.

The mechanisms determining which parental haplotype is selected in (CBA X B10) (k X b)F1 female mice for major histocompatibility complex (H-2) restricted, male-specific (H-Y), immune, cytotoxic T-cell (Tc-cell) responses, was investigated. The data show that haplotype preference is variable, and may be directed towards one, both, or neither of the parental haplotypes. This preference is reflected in the precursor or frequency of memory Tc cells as measured by limiting dilution assays. It was further shown that maternal influence, antigen dose, route of immunization, and a feedback mechanism on the stimulator cells in vivo could not influence haplotype preference or its observed variability. Evidence for cross-reactive killing by H-2k and H-2b H-Y immune Tc cells on H-2b and H-2k allogeneic targets, respectively,, (i.e., the independent haplotype of the other parent of the F1 mice), provide evidence for natural tolerance as a possible mechanism to explain haplotype preference.

Animals↗
PubMed1981

Specific haplotype preference in congenic F1 hybrid mice in the cytotoxic T cell response to the male specific antigen H-Y.

Haplotype preference in the cytotoxic T cell response to H-Y in B10 congenic mice is only found in (B10 X B10.S)F1 hybrids. (B10 X B10.BR)F1 and (B10 X B10.D2)F1 do not generally show haplotype preference. H-2s is the preferred haplotype in H-Y immune (B10 X B10.S)F1 Tc cells. This haplotype preference is antigen specific since no preference was observed in the anti-influenza responses in (B10 X B10.S)F1 hybrids. Feedback inhibition as an explanation for haplotype preference could be excluded, but cross-reactivity of B10 H-Y immune Tc cells on B10.S targets suggests that natural tolerance may be responsible for haplotype preference.

Animals↗
PubMed1981

Analysis of the cytotoxic T cell response to H-Y in CBA/H mice.

The dose response, kinetics, and target cell specificity of the H-Y immune Tc-cell response of fp-primed CBA/H mice was analyzed. Non-MHC genes were shown to influence responsiveness in fp-primed H-2k strains of mice. The possibility that dominant T-suppressor cells mask responsiveness in i.p. primed CBA/H mice was not confirmed in mixing experiments. Female spleen-adherent cells injected with male spleen cells i.p. elicited H-Y immune Tc-cell responses.

Animals↗
PubMed1980

Cytotoxic T-cell response to H-Y in 'non-responder' CBA mice.

Murine cytotoxic T-cell (Tc cell) responses to various antigens are controlled by immune response genes (Ir) mapping in the major histocompatibility complex (H-2). Both helper T cells, controlled by I region-coded genes, and Tc cells, controlled by K/D antigens, are necessary for a positive response. An H-2-restricted Tc-cell response to the male specific minor transplantation antigen (H-Y) can be elicited in B10 (H-2b) female mice primed with syngeneic male spleen cells intraperitoneally (i.p.) or intravenously (i.v.), or by skin grafting followed by restimulation in vitro in mixed lymphocyte culture (MLR) with male cells. CBA (H-2k) mice do not respond by these routes of in vivo priming, and this was thought to be due to a lack of permissible Ir genes for helper function. However, we now report that subcutaneous hind-footpad (fp) immunisation of 'non-responder' CBA mice with syngeneic male cells changes them to responders, a result which argues against a generalised Ir gene-controlled helper defect.

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