EXPRESSION OF STRONG Mls DETERMINANTS IN
نویسنده
چکیده
Although typical mixed lymphocyte reactions (MLR) 1 are directed predominantly to H-2 determinants , high pr imary MLR in mice can also be elicited by gene products o f the minor lymphocyte-stimulating (Mls) locus located on chromosome 1 (1). O f the four described Mls alleles, a b c d, Mis a and Mls d determinants elicit the strongest response. Since these two sets of determinants cross-react extensively (and are probably indistinguishable), we shall re fer to them as "Mls a'd determinants" (2). Mis a'd de terminants are o f interest for at least three reasons. Firstly, in our hands the T cell response to these determinants does not exhibit H-2 restriction (3, 4) (although others disagree with this viewpoint [5]). Secondly, f rom studies on karyotypically unstable hybridomas prepared f rom a dual-reactive T cell clone, we have prel iminary evidence that the receptors for allo-H-2 and Mls a'd determinants are encoded on dif ferent chromosomes. 2 Thirdly , the expression of MIs a'd determinants appears to define one of the two subsets of B cells, namely the "mature" B cells, which develop late in ontogeny and express Lyb 5 surface alloantigens (6); immature (Lyb 5-) B cells do not express Mls a'd determinants. Mls a'd determinants are thus a potentially useful marker for probing the functional differences between mature and immature B cells, and for addressing the key issue of whether these two subsets of cells represent distinct lineages or different stages of differentiat ion o f the same lineage. Much of the evidence on the differences between mature and immature B cells has come f rom studies on B cell development in CBA/N mice, i.e., mice expressing X-linked immunodefic iency (xid) (6). These mice contain immature This work was supported by National Science Foundation grant 8303042 and National Institutes of Health grants CA-15822, CA-33958, and AI-10961. The present address of S. R. W. and J. s. is Dept. of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA 92037. Abbreviations used in this paper: FCS, fetal calf serum; LN, lymph node; MLR, mixed lymphocyte reactions; MLS, minor lymphocyte-stimulating; PFC, plaque-forming cells; TDL, thoracic duct lymphocytes; TNP, trinitrophenyl; xid, x-linked immunodeficiency. 2 T cell hybridomas with dull reactivity for MIs ~'d and allo H-2 determinants can selectively lose one specificity. Webb, S. R.,J. Hu Li, I. MacNeil, P. Marrack,J. Sprent, and D. B. Wilson. Manuscript in preparation.
منابع مشابه
BriefDefinitive Report Mls IS NOT A SINGLE GENE, ALLELIC SYSTEM Different Stimulatory Mls Determinants Are the Products of at Least Two Nonallelic, Unlinked Genes
The set of cell surface determinants encoded by the MHC is remarkable in that it is recognized by naive T cell populations at a sufficiently high precursor frequency to induce substantial primary proliferative responses, and the critical biologic role played by MHC products has been well established . The only other determinants capable of inducing strong proliferative responses by naive T cell...
متن کاملCD8+ T cell response to Mls-1a determinants involves major histocompatibility complex class II molecules
Recent studies indicate that both CD4+ and CD8+ T lymphocytes proliferate in vitro in response to Mls-1a-encoded determinants. Using both immunogenetic and antibody blocking approaches we show here that Mls-1a responses of both subsets require expression of major histocompatibility complex (MHC) class II molecules (I-A and/or I-E) by the stimulator cells. Furthermore, CD8+ T cell responses to M...
متن کاملMls is not a single gene, allelic system. Different stimulatory Mls determinants are the products of at least two nonallelic, unlinked genes
Mls determinants share with MHC products the unique property of stimulating T cells at extraordinarily high precursor frequencies. The Mls system was originally described as a single locus on chromosome 1, with four alleles, Mlsa, Mlsb, Mlsc, and Mlsd, that encode polymorphic cell surface structures. However, the fundamental issues of polymorphism and allelism in the Mls system remain controver...
متن کاملClonal analysis of the Mls system. A reappraisal of polymorphism and allelism among Mlsa, Mlsc, and Mlsd
Only two sets of antigenic determinants are recognized by T lymphocytes at uniquely high precursor frequencies: those encoded by the MHC and those encoded by Mls. The structural as well as functional characteristics of MHC products have been extensively analyzed. In contrast, little information concerning the nature of Mls genes or their products is available. Although it was originally describ...
متن کاملCD4 expression is differentially required for deletion of MLS-1a- reactive T cells
Clonal deletion of thymocytes expressing potentially self-reactive T cell receptors (TCRs) occurs during thymocyte ontogeny. Mice deficient for CD4 expression provide a unique model system to study the contribution of the CD4 molecule in negative selection of T cells reactive against the major histocompatibility complex class II-associated retroviral self-superantigen, Mls-1a. In the presence o...
متن کامل