Genetic control of autoimmune encephalomyelitis and recognition of the critical nonapeptide moiety of myelin basic protein in guinea pigs are exerted through interaction of lymphocytes and macrophages.
Genetic control has been studied of the response to the encephalitogenic nonapeptide (NP) determinant of myelin basic protein (BP) in inbred guinea pigs of strains resistant or susceptible to induction of experimental autoimmune encephalomyelitis (EAE). By studying bone marrow-reconstituted animals, we found that susceptibility to induction of EAE was a function of the genotype of the cells of the lymphohematopoietic system and not of the physiological environment or target organ. Analysis of the T cell response showed that susceptible strains 13 or (2 X 13)F1 hybrid guinea pigs recognized the NP determinant when injected with whole BP in adjuvant. Resistant strain 2 guinea pigs responded to undefined determinants on BP, but not to the NP moiety. We investigated the cells involved in regulating the response to the NP determinant by injecting susceptible F1 hybrids with BP-pulse macrophages of either parental strain. Susceptible strain 13 macrophages triggered a response to the NP determinant and induced clinical EAE. In contrast, F1 animals injected with resistant strain 2 macrophages failed to respond to the NP determinant, although the macrophages were capable of presenting other undefined determinants present on whole BP. Therefore, genetic control of the immune response to the NP determinant appears to be exerted at the level of antigen presentation by macrophages to T lymphocytes.
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics*; D016026:Bone Marrow Transplantation; D002450:Cell Communication; D003433:Crosses, Genetic; D004679:Encephalomyelitis / Q000235:genetics*; D000939:Epitopes; D005838:Genotype; D006168:Guinea Pigs; D006824:Hybridization, Genetic; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology
D000939:Epitopes; D004676:Myelin Basic Protein; D010455:Peptides; D014373:Tuberculin