Cooperation across the histocompatibility barrier

Waldmann, Herman; Pope, Heather; Munro, Alan

doi:10.1038/258728a0

Cited by 42 publications

(14 citation statements)

References 9 publications

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“…Our results lead us to several conclusions . First of all they confirm our previous findings (4,5,11,17) Our results are consistent with several previous reports on the properties of T cells raised in chimeric mice in which the authors concluded that I-region restrictions on T-cell/B-cell interactions were not inherent in the genotype of the helper T cell (27,28) . The present study confirms this conclusion and extends it to cover an Ir gene controlled response .…”

Section: Discussionsupporting

confidence: 93%

The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression.

Kappler¹,

Marrack²

1978

The Journal of Experimental Medicine

131

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We have studied the properties of helper T cells specific for sheep erythrocytes (SRBC), keyhole limpet hemocyanin (KLH), or poly-L-(Tyr,Glu)-poly-DL-Ala-poly-L-Lys [(T,G)-A--L]. These T cells differentiated and were primed in vivo in irradiation chimeras constructed of various combinations of F1 and parental bone marrow donors and irradiated recipients. Primed T cells were then tested for helper activity in the in vitro response of B cells and macrophages (Mphi) of parental or F1 origin to the hapten trinitrophenol coupled to the priming antigen. When testing either SRBC or KLH-specific T cells of parental H-2 type which had differentiated in F1 hosts, we found that they cooperated equally well with B cells and Mphi of either parental H-2 type. On the other hand, when testing F1 T cells which had differentiated in parental hosts, we found that they cooperated well only with B cells and Mphi which had the K-IA region type of the parental host. In similar experiments we found that (T,G)-A--L-specific T cells of low responder H-2 type which had differentiated in (high responder X low responder) F1 hosts induced high responses in high responder B cells and Mphi (T,G)-A--L-specific F1 T cells which differentiated in high responder but not those which differentiated in low responder hosts induced high responses in high responder B cells and Mphi. Low responder B cells and Mphi yielded low responses in all cases regardless of the source of (T,G)-A--L-specific T cells with what they were tested. Our results support the conclusion that I-region and Ir genes function via their expression in B cells and Mphi and in the host environment during helper T-cell differentiation, but not, at least under the conditions of these experiments, via their expression in the helper T cell itself. These findings place constraints upon models which attempt to explain the apparent dual recognition of antigen and I-region gene products by helper T cells.

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Section: Discussionsupporting

confidence: 93%

The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression.

Kappler¹,

Marrack²

1978

The Journal of Experimental Medicine

131

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“…In contrast to the preceding results, helper T cells from A/J ~ CAF1 chimeras showed clear disparities in their ability to provide helper activity for certain of the B-cell types. Thus, while effective help was provided to conventional CAF1 and A/J and to chimeric CAF1 ~ CAF1, A/J CAFa and CAF1 ~ A/J B cells, little or no demonstrable helper activity was provided for B cells derived from either conventional BALB/c (group 19) or BALB/c ~ CAF1 (group 22) chimera donors. These results indicate quite clearly that T cells in the A/ J ~ CAF1 chimera retain the phenotype of the original parental strain in terms of genetic restriction in their cooperative activity (2,3).…”

Section: Caf1 Helper T Cells (Fig 2) Conventional Cafa Helper T Celmentioning

confidence: 99%

“…The validity of the original interpretation of the basis for genetic restrictions dictating the most effective interactions between T and B lymphocytes in the development of antibody responses came under question amidst the reports of other investigators who failed to find similar restrictions in different systems in which T-B-cell cooperative responses were analyzed (17)(18)(19); more recent studies in these very same laboratories have clarified these matters somewhat (20)(21)(22). The most compelling of such experiments were those performed with cells obtained from tetraparental bone marrow chimeric mice (17).…”

mentioning

confidence: 99%

Adaptive differentiation of murine lymphocytes. I. Both T and B lymphocytes differentiating in F1 transplanted to parental chimeras manifest preferential cooperative activity for partner lymphocytes derived from the same parental type corresponding to the chimeric host.

Katz¹,

Skidmore²,

Katz³

et al. 1978

The Journal of Experimental Medicine

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Approximately 5 yr ago the first observations that documented genetic restrictions imposed by genes within the major histocompatibility complex (MHC) 1 upon cooperative interactions between T lymphocytes and macrophages and between T lymphocytes and B lymphocytes were described (1-3). Later, it was found that the most efficient lysis of target cells by specific cytotoxic T lymphocytes (CTL) occurred when the CTL and target cell, respectively, shared gene identities in the mouse H-2 complex (4-8). Genetic mapping studies documented that gene(s) controlling T-B-cell interactions are located in the/-region of the mouse 1-1-2 complex (9), whereas those involved in CTL-target interactions are located in the K and D regions of/_/. 2 (10, 11).The subject of MHC-linked genetic restrictions on cell-cell communication processes has evoked controversy both in terms of the extent of such constraints on cell-cell interactions and on the best possible interpretations of such restrictions (12-14). Essentially two major concepts have evolved to explain these genetic restrictions on cell interactions. The first hypothesis, which stemmed from analysis of such restrictions in T-B-cell interactions, considered that interactions among various cell types in the immune system are mediated by cell interaction (CI) molecules located on the cell surface, at least some of which are encoded by MHC genes (i.e./-region genes in this case), and which are quite distinct from the lymphocyte receptors specific for conventional antigens (13-15). The CI molecule concept therefore emphasizes a dual recognition mechanism which involves at least two distinct molecular interactions in lymphocyte activation, one utilizing antigen-specific receptors and the second consisting of reactions between the relevant CI structures and their corresponding receptors. The second major concept, derived primarily from studies in the CTL systems, considered that T lymphocytes have receptors which recognize not antigen alone, but antigen in some form of association with MHC gene products on cell surface membranes; this concept of "ahered-setf" (16) recognition by T lymphocytes differs substantially from the CI molecule concept in predicting the existence of a single receptor on T cells simultaneously recognizing modified determinants on the cell surface. To date, no definitive proof has been obtained to establish which of these two models is correct.

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“…Although the suppressive effects of allogeneic T cells have been appreciated for some time, simple in vitro systems allowing the systematic study of negative aliogeneic effects have only recently been exploited (Epstein & Cohn, 1977, Swain & Dutton, 1977a, Swain et al, 1976, Waldmann et al, 1976. These systems indicate that potent suppression results even when unprimed T eels confront responding B cells which differ at the MHC.…”

Section: A Llosuppressionmentioning

confidence: 99%

Alloreactivity, the Development of the T Cell Repertoire and the Understanding of T Cell Function

Dutton

Panfili

Swain

1978

Immunological Reviews

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Cooperation across the histocompatibility barrier

Cited by 42 publications

References 9 publications

The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression.

The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression.

Adaptive differentiation of murine lymphocytes. I. Both T and B lymphocytes differentiating in F1 transplanted to parental chimeras manifest preferential cooperative activity for partner lymphocytes derived from the same parental type corresponding to the chimeric host.

Alloreactivity, the Development of the T Cell Repertoire and the Understanding of T Cell Function

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