Date of Award

Winter 1980

Project Type

Dissertation

Program or Major

Genetics (Animal Sciences)

Degree Name

Doctor of Philosophy

Abstract

Cross-reactivity between major histocompatibility complex (MHC) antigen and Rous sarcoma virus (RSV)-induced tumor associated antigen (TAA) in chickens was investigated. The B erythrocyte allcantigen locus was the genetic marker for the MHC. B2B2 and B5B5 chickens from crosses of highly inbred lines 6-1 and 15-1 and B24B24 chickens from noninbred line UNH 105 were used.

B2B2 chickens rendered partially tolerant to B5 antigen through multiple intraperitoneal inoculations of either viable or lysed white blood cells (WBC) or viable red blood cells (REC) from B5B5 chickens had a significantly higher incidence of tumor progression than untreated, phosphate buffered saline treated, or B2B2 WBC inoculated B2B2 chickens. The criteria of tolerance were absence of antibody to the cell type inoculated and acceptance of skin allografts from B5B5 donors by B2B2 chickens. The higher incidence of tumor progression did not result from a non-specific effect of graft versus host activity (GVH) because GVH activity was present only in chickens inoculated with B5B5 viable WBC. B5 antigen-TAA cross-reactivity was indicated because B2B2 chickens partially tolerant to B5 antigen were also tolerant to RSV-induced tumor, as shown by an increased incidence of tumor progression. Since WBC and REC share B-F antigens, and both were involved in producing the partial tolerance, the B-F region of the MHC was implicated in the cross-reactivity.

Cross-reactivity was also observed when lymphocytes from B2B2 chickens bearing RSV-induced tumors lysed in vitro targets of B2B2 and B5B5 RSV-infected chicken embryo fibroblasts (CEF) and B5B5 normal CEF, but did not lyse B2B2 and B24B24 normal CEF. Lymphocytes from normal B2B2 chickens did not lyse any of the five types of CEF targets. Cross-reactivity was observed yet again when absorption with B2B2 RSV-infected CEF significantly lowered the titer of B2B2 anti-B5B5 alloantisera. Alloantisera absorption studies also showed that both RSV-infected and uninfected CEF shared alloantigens, in particular B-F allcantigens, with syngeneic RBC's further supporting the idea that B-F antigen is involved in the cross-reactivity.

Cross-reactivity was not observed in the IgG from chickens bearing RSV-induced tumors. Moreover, use of three techniques of immunization of B2B2 chickens with B5B5 cells did not increase the incidence of tumor regression in the immunized chickens, and provided no evidence of cross-reactivity. Although humoral immunity was observed in these two studies, cell-mediated immunity may be relatively more important in tumor regression and the focus of cross-reactivity.

Based upon these findings it is hypothesized that B5B5 RSV-induced tumor bearing hosts respond poorly to tumor partially because B5 antigen cross-reacts with TAA. B5B5 individuals, therefore, may have difficulty recognizing RSV-induced tumor as foreign and this severely limits the development cf an effective anti-tumor immunity. Either TAA or a TAA-E2 antigen complex may cross-react with E5 antigen. Cross-reactivity involving cell-mediated immunity may make the difference between tumor regression and progression.

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