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Genetic polymorphism in the H-2:Qa:Tla region of chromosome 17 is associated with constitutive variation of bodily odor phenotypes which permit individual olfactory recog-. nition among mice. To determine whether known genes in the H-2: Qa: Tia complex are concerned in the constitution-of odor phenotypes, mice were tested for their ability to sense a difference between the B6/By (H-2b) and congeneic B6.C-H-2b" strains, which differ genetically by mutation of the H-2K gene. As in previous studies of the. sensory discrimination of H-2:Qa:Tla phenotypes, mice were trained by reward in a Y maze to distinguish the odors of urine samples, and the successful distinctions of B6/ By from B6.C-H-2b"' were confirmed by transfer of training, without reward, to coded samples of urine from genetically equivalent urine donor mice which the trained mice had not previously encountered. Cosegregation of odor phenotype with H-2b and H2bml was demonstrated by transfer of training to typed H-2b and H-2bml homozygous segregants of F2 generations of appropriate crosses. Although it is not excluded that the differences in odor phenotype which distinguish H-2b and H-2b1" mice are directly, related to the structure of the H-2b and H-2bml products, it is equally possible that H-2-related odor phenotypes arise from effects of H-2 genetic variation on metabolic pathways either directly, or indirectly through developmental polymorphism.

Receptors of effector T lymphocytes of congeneic strains of mice do not recognize public H-2 specificities and react to private H-2 specificities only. This has been established with the use of three tests: direct cytotoxicity assay of immune lymphocytes upon target cells, specific absorption of the lymphocytes on the target cells, and rejection of skin grafts at an accelerated fashion. Immunization with two private H-2 specificities in the system C57BL/10ScSn leads to B10.D2 induces formation of two corresponding populations of effector lymphocytes in unequal proportion: a greater part of them is directed against the private specificity H-2.33 (Kb), while the smaller part is towards H-2.2 (Db) private specificity. These two populations of effector lymphocytes do not overlap, as demonstrated by experiments on their cross-absorption on B10.D2 (R107), B10.D2 (R101), B10.A(2R), and B10.A(5R) target cells, as well as on mixtures of R107 and R101 targets. Following removal of lymphocytes reacting with one of the private H-2 specificities, lymphocytes specific to the other specificity are fully maintained. A mixture of target cells, each bearing one of the two immunizing private specificities, absorbs 100% of the immune lymphocytes and is totally destroyed by them. It is suggested that H-2 antigens are natural complexes of hapten-carrier type, in which the role of hapten is played by public H-2 specifities and that of the carrier determinant by either private H-2 specificities or structures closely linked to them. Various models of steric arrangement of MHC determinants recognized by receptors of effector T lymphocytes are discussed.

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Young mice of the strains A/Y and B10.D2 were repeatedly treated with diethylsulphate (DES) in different doses (36 to 1100 mg/kg). At the age of 9 weeks they were mated to females of the strains A. CA (' A' group) and C57BL/10Eg ('D' group) respectively. 2101 progeny of these matings were tested for histocompatibility by skin grafting. The spontaneous Hmutation rates were 6-96 x 10~4 per gamete in the A group and 9-6 x 10~4 per gamete in D group. In progeny of treated males the H-mutation rates were 0 in A group and 5-79 x 10~3 per gamete in D group, showing apparent effect of paternal DES treatment on mutation frequency in the last group. Two mutations of the H-2 locus were found, which together with the other three H-2 mutations published so far yielded a mutation rate of 5-18 x 10~* per gamete. The mutation rate of the H-2 locus is higher than the expected rate perH-locus, indicating a great genetic complexity of H-2.

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Tumor escape from the host immune response remains the major problem holding the development of immunotherapies for cancer. In this review, congenic mouse lines are discussed that differ dramatically in their ability to respond to tumors tested and, thereby, to survive or to succumb to the tumor and/or its metastases. This ability is under the control of either MHC class I or nontrivial MHC class II beta genes expressed in a small subpopulation of antigen-presenting cells. Two hypotheses can explain the results obtained so far: (1) emergence of tumor cell variants that escape the host immune response in morbid mice but are eliminated in survivors, and (2) tumor-induced immunosuppression, which is either efficient or not, depending on the congenic line used. It is argued that further experimentation on these congenics will allow to choose the correct hypothesis, and to characterize the mechanism(s) of elimination of minimal residual disease and prevention of tumor escape by the immune system of survivors as well as the reason(s) for its failure in morbid mice. It is also argued that the use of these models will substantially increase the chance to resolve the controversy of poor correlation of immunotherapy testing in mice with clinical results.