Epitope recognition and T cell receptors in recurrent autoimmune anterior uveitis in Lewis rats immunized with myelin basic protein.
Lewis rats immunized with myelin basic protein (MBP) develop experimental autoimmune encephalomyelitis (EAE) and associated anterior uveitis (AU). Rats recover and become resistant to further reinduction of EAE. We investigated whether the resistance to reinduction of EAE was associated with the resistance to AU in LEW rats reinjected with MBP. We demonstrated that while rats remained resistant to EAE, they become susceptible to uveitis after recovery, and suffered a second episode of disease. The susceptibility to reinduced disease was associated with the recognition of new MBP epitopes. In contrast to the initial episode of AU, TCR Vbeta8.2 predominance was not observed in the iris/ciliary body. Our results suggest that T cells specific for MBP, which are rapidly reactivated when re-exposed to antigen, are sufficient to induce clinical uveitis in LEW rats. This process may involve a shifting of T cell specificity from the major encephalitogenic peptide utilizing the Vbeta8.2 receptor to a more diverse cell repertoire.
Adamus
G
G
Neurological Sciences Institute, Oregon Health Sciences University, Mailing Code L-111, Portland, OR 97201, USA. adamusg@ohsu.edu
Manczak
M
M
Sugden
B
B
Arendt
A
A
Hargrave
P A
PA
Offner
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002924:Ciliary Body / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D007114:Immunization; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D012008:Recurrence; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014606:Uveitis, Anterior / Q000235:genetics / Q000276:immunology* / Q000473:pathology*
D018984:Epitopes, T-Lymphocyte; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell