The J alpha segment contributes to the affinity of V beta 6+ cells for vSAG-7 (Mls-1a) presented by I-A molecules.

Recognition of superantigens (SAG) by T cells is major histocompatibility complex (MHC) dependent but not MHC restricted. In the case of vSAG-7 (Mls-1a), encoded by the Mtv-7 provirus, I-E molecules play a dominant role in the vSAG-7-MHC-T-cell receptor (TCR) interaction, the I-A molecule being less important. vSAG-7 is recognized predominantly by T cells bearing the V beta 6 element, which are deleted in Mtv-7+ mice; this deletion is nearly complete in mice expressing I-E molecules, but only partial in mice expressing exclusively the I-A molecules of permissive haplotypes. In view of these data, we hypothesized that vSAG-7-specific V beta 6+ T cells have a large spectrum of affinities for the MHC-vSAG-7 complex and that all of them, even those with a relatively low affinity, recognize the I-E-vSAG-7 complex, while only those with high affinity can recognize the I-A-vSAG-7 complex. Fourteen CD4 V beta 6+ vSAG-7-specific clones were studied and classified into three groups of avidity, depending on their interactions with different I-E- I-A(+)-vSAG-7 permissive haplotypes. Sequencing of the alpha and beta chains of their TCR suggested that the affinity for the vSAG-7 is influenced by the J alpha element. Four out of six low-affinity T-cell clones possessed the transcript for the J alpha 34 segment. Furthermore, five out of six low-affinity T-cell clones had the GGSN sequence in their CDR3 alpha, while the sixth low affinity clone had the conservative substituted SGGN sequence. These results strongly suggest that the expression of the J alpha 34 segment confers a very weak reactivity to T cells recognizing vSAG-7.

Influence of a bovine spleen extract on immunological responses in mice.

The presence of immunological stimulatory and inhibitory activities has been detected in a bovine spleen extract F prepared by acetic extraction of an acetonic powder. F was fractioned after water dilution, by ultrafiltration on an Amicon PM-10 membrane. Two successive ultrafiltrates (mol. wt. less than 10,000) are obtained: U1 which contained the largest pool of the low molecular weight substances, and U2 which was shown previously to be enriched in an immunosuppressive peptide. The biological activities of U1 have been studied compared to those of U2: 1. Added to mouse spleen cells culture, U1, at low dose, stimulated 3H-thymidine incorporation into the DNA of the cells, but inhibited it when large dose was added. In this test, U2 was devoid of stimulatory action. 2. When injected into mice sensitized with sheep red blood cells, three distinct activities were detected: U1 was inhibitory at the sensitization period; at the last step of differentiation of the lymphocyte, U1 was stimulatory at low dose and inhibitory at large dose. As assessed by Biogel P-2 chromatography, this last activity was attributed to the presence in fraction U1 of the immunosuppressive peptide previously characterized in U2.

Immunosuppressive activity of a purified spleen extract (lymphocytic chalone?) is not due to polyamines spermine and spermidine.

Spermine, spermidine and a purified spleen extract (PSE) have been compared in vivo in these three tests: hemolytic plaque forming capacity in sensitized mice, delayed hypersensitivity reaction and 3H-thymidine incorporation into various tissue cells. The results obtained demonstrated that the immunosuppressive activity of PSE cannot be attributed to those polyamines. Ion exchange analysis of PSE before and after acid hydrolysis confirmed the absence of free and/or bound polyamines in the studied extract.

Purification of immunosuppressive factors extracted from bovine spleen (lymphoid chalone). II. Biological activity.

A highly purified extract from bovine spleen (FA) possessing immunosuppressive capacity was studied. Its tissue specificity was analysed in vivo and in vitro and the main components of FA, the well-known nucleosides deoxycytidine, deoxyinosine and thymidine, were tested in vivo. It seems that the molecule responsible for the biological activity of FA is a new substance endowed with strong specific activity and that lymphoid tissue is highly sensitive to the inhibiting capacity of this purified fraction.