Immunogenetics

Stankus, Richard P.; Leslie, Gerrie A.

doi: 10.1007/bf01576939pmid: N/A

Interstrain analysis of the humoral response of rats to streptococcal group A carbohydrate (SACHO) 1, employing seven inbred strains representing six histocompatibility haplotypes at the Ag-B locus, suggests that the immune response genes to SACHO are not linked to the major rat histocompatibility locus. The low-precipitin response of all seven inbred rat strains was similar to the precipitin response of F7 Sprague-Dawley rats selectively bred for a low-precipitin response to SACHO. Although strain differences were not apparent in the magnitude of the precipitin response to SACHO, the qualitative expression of anti-SACHO antibodies with restricted heterogeneity was more frequently observed in the August strain of rats than in the six other inbred strains examined. Cross-idiotypic specificity was demonstrated for anti-SACHO antisera obtained from nine inbred rat strains. The observations on idiotypy favor the importance of germ-line genes coding for rat antibody variable region determinants in response to SACHO.

Black, Paul L.; Marsh, David G.; Jarrett, Esther; Delespesse, Guy J.; Bias, Wilma B.

doi: 10.1007/bf01576967pmid: N/A

In 76 members of 13 large families, we investigated whether association exists between specific familialHLA haplotypes and immune responsiveness to four different highly purified pollen antigens (ragweed antigens E, Ra3, and Ra5 and rye grass Group I). Specific immune response was studied quantitatively by measurement of IgE-mediated skin sensitivity, serum IgG antibody, and antigen-induced lymphocyte proliferationin vitro. We found no evidence for association between specificHLA haplotype and specific response measured by any one or more of our indices of immune function. In several families we found evidence of specific response in one generation but not in another. We found a number of instances of individuals exhibiting lymphocyte responsiveness to an antigen, but no detectable specific IgE or IgG antibody. Surprisingly, we also found a few cases of individuals with marked IgE and/or IgG responses to a given antigen who showed no measurable lymphocyte responsiveness to that antigen, despite lymphocyte responsiveness to other nonimmunologically crossreacting antigens. In several cases, we also observed lymphocyte stimulation and serum IgG antibody, but no detectable IgE response. Our results conflict with previous investigators' reports of “linkage” betweenHLA haplotype and specific IgE-mediated skin sensitivity in families.HLA- linked immune response (Ir) loci may exist in humans, but genetic complexity and the limits of current technology preclude our ability to demonstrate their existence.

Doherty, Peter C.; Götze, Dietrich; Trinchieri, Giorgio; Zinkernagel, Rolf M.

doi: 10.1007/bf01576981pmid: N/A

Virus-immune effector T cells generated in vivo are specific for both the virus used and theH-2 type of the infected mouse. Genes mapping at H-2K or H-2D apparently serve as self markers. The mechanism underlying this function is, however, not understood. This paper summarizes models that seem, at present, to be feasible explanations for this phenomenon, and considers possible implications of the hypothesis that self-recognition may be mediated by way of the same V gene subset that codes for alloreactivity.

Blanden, R. V.; Dunlop, M. B. C.; Doherty, P. C.; Kohn, H. I.; McKenzie, I. F. C.

doi: 10.1007/bf01576984pmid: N/A

Lysis of ectromelia- or LCM virus-infected macrophage target cells by virus-specific cytotoxic T cells from mice immunized with the homologous virus occurred only where donors of T cells and target cells shared eitherH-2K orH-2D genes. With both viruses, use of T cell or target cell donors bearing mutations (B6.C-H-2ba, B6-H-2bh, B6-H-2bg1, and B6-H-2bg2), all of which apparently occurred in the same single genetic element in theH-2Kb region, abolished (H-2ba) or impaired (H-2bh,H-2bg1 andH-2bg2) lysis in T cell-target cell combinations that shared (apart from the mutations) all other genes in theK, I-A, orI-B regions of theH-2 complex. The data suggest that virus-induced antigenic patterns on infected B6.C-H- 2ba (mutant) cells are more different antigenically from those on C57BL/6 (wild type) cells than are those on infected cells from the other mutants -B6-H-2bh, B6-H-2bg1, and B6-H-2bg2. (B6.C-H-2ba× B6 -H-2bh)F1 mice behaved like B6-H-2bh, indicating no complementation, and confirming that theH-2K gene(s) involved in recognition of virus-infected cells by virus-specific T cells behave as a single element. These findings are discussed in relation to the nature of virus-induced antigenic patterns that are recognized by virus-specific cytotoxic T cells.