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The autoreactive T cells that escape central tolerance and form the peripheral self-reactive repertoire determine both susceptibility to autoimmune disease and the epitope dominance of a specific autoantigen. SJL (H-2(s)) mice are highly susceptible to the induction of experimental autoimmune encephalomyelitis (EAE) with myelin proteolipid protein (PLP). The two major encephalitogenic epitopes of PLP (PLP 139-151 and PLP 178-191) bind to IA(s) with similar affinity; however, the immune response to the PLP 139-151 epitope is always dominant. The immunodominance of the PLP 139-151 epitope in SJL mice appears to be due to the presence of expanded numbers of T cells (frequency of 1/20,000 CD4(+) cells) reactive to PLP 139-151 in the peripheral repertoire of naive mice. Neither the PLP autoantigen nor infectious environmental agents appear to be responsible for this expanded repertoire, as endogenous PLP 139-151 reactivity is found in both PLP-deficient and germ-free mice. The high frequency of PLP 139-151-reactive T cells in SJL mice is partly due to lack of thymic deletion to PLP 139-151, as the DM20 isoform of PLP (which lacks residues 116-150) is more abundantly expressed in the thymus than full-length PLP. Reexpression of PLP 139-151 in the embryonic thymus results in a significant reduction of PLP 139-151-reactive precursors in naive mice. Thus, escape from central tolerance, combined with peripheral expansion by cross-reactive antigen(s), appears to be responsible for the high frequency of PLP 139-151-reactive T cells.

Blood leukocytes from cattle with bovine ocular squamous cell carcinoma (BOSCC) react with extracts of BOSCC, and blood leukocytes from cattle with cutaneous papillomas react with extracts of papillomas in the erythrocyte rosette (E-rosette) augmentation test. Sera from cattle with BOSCC, with cutaneous papillomas, and with ocular papillomas and sera from lesion-free cattle were tested for their ability to block antigen-induced E-rosette augmentation and E-rosette augmentation induced by phytohemagglutinin. Autologous serum from 16 BOSCC-affected cattle blocked E-rosette augmentation induced by BOSCC extract, and autologous sera from three cattle with cutaneous papillomas blocked E-rosette augmentation induced by papilloma extract. Sera from cattle with BOSCC did not block E-rosette augmentation induced by papilloma extract, nor did sera from cattle with cutaneous papillomas block BOSCC extract-induced E-rosette augmentation. Sera from cattle with BOSCC blocked BOSCC extract-induced E-rosette augmentation in some but not all allogeneic combinations. E-rosette augmentation was observed when blood leukocytes from all 12 BOSCC-affected and six control cattle were exposed to phytohemagglutinin. This reaction was blocked by autologous sera from 11 of the 12 BOSCC-affected cattle, from one of the three cattle with cutaneous papillomas, but from none of the three other cattle. Sera from BOSCC-affected cattle also blocked phytohemagglutinin-induced E-rosette augmentation in allogeneic combination, regardless of the tumor status of the donor of the leukocytes.