Effects of the major histocompatibility complex loci and T-cell receptor beta-chain repertoire on Theiler's virus-induced demyelinating disease.
We have investigated the potential effects of H-2 and T-cell receptor (TCR) V beta family genes on induction of T-cell immunity and susceptibility to virally induced demyelinating disease by using BALB.S (H-2K(s)A(s)D(s)) and BALB.S 3 R (H-2K(s)A(s)D(d)/L(d)) mice. These parameters were compared with those of highly susceptible SJL/J (H-2K(s)A(s)D(s)) mice that contain only one-half of TCR V beta family genes compared with the above-mentioned strains. Our results demonstrate that BALB.S but not BALB.S 3 R mice are susceptible similar to SJL/J mice. Although the level of CD4(+) T-cell infiltration to the CNS was elevated in susceptible mice, virus-specific immune responses restricted with H-2(s) were similar in these mice. No preferential use of V beta families associated with differences in the major histocompatibility complex (MHC) components was apparent. However, the pattern and sequence of CDR 3 distribution shows T-cell clonal accumulation in the CNS associated with the H-2 components. Further anti-CD8 antibody treatment of resistant BALB.S 3 R mice abrogated resistance to demyelinating disease, indicating that CD8(+) T cells restricted with H-2D(d)/L(d) are most likely to exert resistance in BALB.S 3 R mice. These studies indicated that TCR V beta and MHC class II genes are the secondary to a particular MHC class I gene expression in susceptibility to virally induced demyelinating disease.
Kim
Byung S
BS
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Il 60611, USA. bskim@northwestern.edu
Mohindru
Mani
M
Kang
Bongsu
B
Kang
Hyun Seok
HS
Palma
Joann P
JP
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018188:Cardiovirus Infections / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis; D003711:Demyelinating Diseases / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000235:genetics / Q000276:immunology; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017945:Theilovirus / Q000528:radiation effects; D015164:Vaccines, Inactivated; D010948:Viral Plaque Assay
D019138:Antibodies, Blocking; D016207:Cytokines; D018076:DNA, Complementary; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015164:Vaccines, Inactivated