H-2Kk and vesicular stomatitis virus G proteins are not extensively associated in reconstituted membranes recognized by T cells.

It is shown that liposomes containing (i) a fluorescein-labeled murine histocompatibility antigen (FITC-H-2Kk) and the G protein of vesicular stomatitis virus or (ii) H-2Kk and fluorescein-labeled viral protein (FITC-G) can elicit H-2-restricted syngeneic antiviral cytotoxic T cells as assayed by 51Cr release from appropriate virus-infected target cells. Fluorescence recovery after photobleaching was used to measure the diffusion coefficients of these reconstituted proteins in four different samples: (i) FITC-H-2Kk; (ii) FITC-H-2Kk and G; (iii) FITC-G; and (iv) FITC-G and H-2Kk. The same rate of lateral diffusion (D = 1 x 10(-8) cm2/sec at 37 degrees C in 25% cholesterol/75% dimyristoylphosphatidylcholine) was obtained in every case. Both proteins, fluorescent as well as nonfluorescent, could be patched by using specific antibodies. When G was patched with antibody, FITC-H-2Kk did not copatch. When H-2Kk was patched with antibody FITC-G did not copatch. These diffusion and patching measurements rule out the possibility that these proteins have either extensive oligomeric associations or strong specific pairwise associations.

Host age and major histocompatibility genotype influence on Rous sarcoma regression in chickens.

The influence of host age and B (major histocompatibility complex) genotype on the fate of Rous sarcoma virus (RSV)-induced tumors was investigated. White Leghorn lines 61 and 151, developed at the Regional Poultry Research Laboratory (RPRL) at East Lansing, MI, and their crosses (F3 to F5) segregating for the B genotype were used. Preliminary experiments with noninbred White Leghorns showed that chickens RSV-inoculated at 4 weeks of age had a significantly lower incidence of tumor regression than chickens RSV-inoculated at 6, 8, 10, 12, and 14 weeks of age. The (61 X 151) F5B2/B2 and B5/B5 chickens inoculated at 6 weeks of age had a lower incidence of tumor regression than (61 X 151)F3 and F4, B2/B2 and B5/B5 chickens RSV-inoculated between 58 and 88 weeks of age, respectively. Some (61 X 151) B2/B2 chickens inoculated between 58 and 88 weeks of age regressed their tumors while all chickens of corresponding genotype inoculated at 6 weeks of age died with tumors. the (61 X 151) B2/B2 chickens had a higher incidence of tumor regression than B5/B5 chickens regardless of age. The genetic RSV-inoculation on the fate of RSV-induced tumors.

Increased growth of RSV-induced tumors in chickens partially tolerant to MHC alloantigens.

Chickens with B2B2 MHC genotypes were made partically tolerant to B5 MHC cell-surface antigens and the fate of their Rous-sarcoma-virus (RSV)-induced tumors was determined. B2B2 chickens partially tolerant to viable or lysed white blood cells (WBC) or viable red blood cells (RBC) from B5B5 chickens had a significantly higher incidence of tumor progression than untreated, PBS-treated, or B2B2 chickens inoculated with WBC from other B2B2 chickens. The criteria for tolerance were absence of antibody titer to the cell type inoculated and acceptance of allografts from B5B5 donors by B2B2 chickens. Graft-vs-host reactions occurred only in B2B2 chickens inoculated with viable WBC from B5B5 chickens. It appears that B2B2 chickens partially tolerant to B5 antigens failed to mount a successful immune response to RSV-induced tumors partly because of a B5 MHC antigen(s) cross-reacted with a tumor associated antigen(s) thereby severely limiting B2B2 host recognition of the tumor as foreign. Since WBC and RBC cell-surface antigens appear to contribute similarly to the effect, the B-F- region of the MHC may be involved.

Cross-reactivity between RSV-induced tumor antigen and B5 MHC alloantigen in the chicken.

Lymphocytes from chickens homozygous (B2B2) at the major histocompatibility complex (MHC) were tested for cytotoxic against five types of target chicken embryo fibroblasts (CEF). Lymphocytes from B2B2 chickens bearing RSV-induced tumors lysed in vitro targets of B2B2 and B5B5 RSV-infected 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. Alloantisera absorption studies showed that both RSV-infected and uninfected CEF shared alloantigens, in particular B-F alloantigens, with syngeneic erythrocytes. Absorption with B2B2 RSV-infected CEF significantly lowered the titer of B2B2 anti-B5B5 alloantisera. Cross-reactivity between B5 antigen(s) and tumor-associated antigen was suggested and the nature of the cross-reactivity was discussed. It is hypothesized that this cross-reactivity prevents B5B5 chickens from recognizing the RSV-induced tumors as foreign, enhances tumor growth and leads to death of the host.

Rous sarcoma regression in seven highly inbred lines of White Leghorns.

Response to Rous sarcoma virus (RSV)-induced tumors was studied in Regional Poultry Research Laboratory (RPRL) lines 61, 63, 72, 100, 151, and 15I5 and in Reaseheath line C, all highly inbred White Leghorn stocks. Virus inoculations were made in chickens at 6 weeks of age. Tumors were scored subjectively for size on a regular basis and in some instances a tumor profile index (TPI) was assigned which characterized tumor development over a 10 week period for each chicken (TPI 1 = complete regression in 28 days; TPI 5 = terminal tumor). The frequency of tumor regression, terminal tumors, and metastases and mean TPI was examined. The incidence of tumor regression ranged from 92% in line 61 to 0 % in lines 151 and 15I5. The frequency of terminal tumors varied from 100% in line 151 to 2% in line61, while metastasis in chickens with terminal tumors differed from 92% in line 15I5 to 0% in line 61. Mean TPI ranged from 2.0 in line 61 to 4.6 in line 15I5 and 4.7 in line C. The erythrocyte alloantigen genotype at the B blood group locus, (part of the B complex, MHC) and 11 additional blood group loci were known for each of the lines. The data indicate that genetic differences in tumor regression may be pronounced between inbred lines which share similar, if not identical, B locus erythrocyte alloantigens and that other unknown genes are also involved.