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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

✍ Scribed by Avraham Ben-Nun; Hanoch Otmy; Irun R. Cohen


Publisher
John Wiley and Sons
Year
1981
Tongue
English
Weight
677 KB
Volume
11
Category
Article
ISSN
0014-2980

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✦ Synopsis


Abstract

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 strain 13 or (2 × 13)F~1~ 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 F~1~ hybrids with BP‐pulsed macrophages of either parental strain. Susceptible strain 13 macrophages triggered a response to the NP determinant and induced clinical EAE. In contrast, F~1~ 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.