Cell interactions between histoincompatible T and B lymphocytes. VII. Cooperative responses between lymphocytes are controlled by genes in the I region of the H-2 complex

346

Helper cell induction to nonparticle antigens in vitro requires the cooperation of T cells and macrophages, but does not occur if the macrophages are allogenic. The reasons for this were investigated. Malfunction of allogenic macrophages was excluded by cultures with their syngenic T cells; suppressor cell induction was excluded by admixture experiments. Thus, T cells and macrophages only cooperated if they were genetically similar. The genetic locus (loci) involved was mapped. Using congenic lines differing only at the H-2 complex, the genetic control of T-macrophage interaction was localized in the H-2 region. Mice with intra H-2 recombinants were used to map the T-macrophage interaction locus in the I-A region of the H-2 complex (formerly known as poly-D, L-ala-poly-L-lys. Recombinants were also used to exclude the presence of another T-macrophage locus either the K, I-B, or I-C, SS-Slp, or D regions of the H-2 complex. Genetic restrictions for T-macrophage interaction in helper cell induction was shown in mice of the H-2-k, d, b, q, s genotypes as well as in H-2 recombinants. The possible mechanisms and significance of this genetic restriction are discussed.

Section: Discussionmentioning

confidence: 99%

“…Genetic restrictions of T-B interaction have been reported and mapped also in the I region (I-A or I-B) (13) . Thus it is possible that the same genes control both T-B and T-macrophage interaction, possibly through the same mediator .…”

Section: Peter Erb and Marc Feldmannmentioning

confidence: 99%

The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens.

Erb¹,

Feldmann²

1975

346

“…In contrast to the wide tissue distribution of the H-2K and H-2D major histocompatibility antigens, the Ia antigens have a restricted distribution with principal expression on subpopulations of T and B lymphocytes (2)(3)(4)(5)(6)(7)(8). The mapping of such important immune functions as mixed lymphocyte reaction, graft versus host reactivities, immune response control (It genes), and cell-cell interaction determinants to the I region has stimulated efforts to identify possible relationships between Ia determinants and these immune functions (9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

Effects of anti-Ia sera on mitogenic responses. II. Differential expression of the Ia marker on phytohemagglutinin and concanavalin A-reactive T cells.

Niederhuber¹,

Frelinger²,

Dine³

et al. 1976

Genes mapping in the I region of the H-2 complex control a system of lymphocyte alloantigens (Ia) which are expressed on a subpopulation of T cells and on most B cells. Specific anti-Ia serum in the presence of rabbit complement removed the splenic T-cell subpopulation responsive to Con-A, but did not affect the response to phytohemagglutinin (PHA) or Leucoagglutinin. Antibodies specific for Ia, H-2K, or H-2D membrane antigens were used without complement to pretreat spleen cells. These antibody pretreated cells responded normally to Con-A and PHA.

“…For the Thelper function, T cells and bone marrow-derived lymphocytes (B cells) clearly require compatibility at the I but not at the K or D region of H-2 (12,13).…”

mentioning

confidence: 99%

H-2 compatibility requirement for virus-specific T-cell-mediated cytolysis. Evaluation of the role of H-2I region and non-H-2 genes in regulating immune response.

Zinkernagel¹,

Dunlop²,

Blanden³

et al. 1976

Lymphocytic choriomeningitis virus (LCMV) and ectromelia virus-specific T-cell-mediated cytotoxicity was assayed in various strain combinations using as targets peritoneal macrophages which have been shown to express Ia antigens. Virus-specific cytotoxicity was found only in H-2K- or D-region compatible combinations. I-region compatibility was not necessary nor alone sufficient for lysis. Six different I-region specificities had no obvious effect on the capacity to generate in vivo specific cytotoxicity (expressed in vitro) associated with Dd. Low LCMV-specific cytotoxic activity generated in DBA/2 mice was caused by the non-H-2 genetic background. This trait was inversely related to the infectious virus dose and recessive. Non-H-2 genes, possibly involved in controlling initial spread and multiplication of virus, seem to be, at least in the examples tested, more important in determining virus-specific cytotoxic T-cell activity in spleens than are Ir genes coded in H-2.