Major histocompatibility complex regulation of the class of the immune response: the H‐2^d haplotype determines poor interferon‐γ response to several antigens

Abstract

The lymph node cells of CBA (H-2k), but not BALB/c (H-2d) mice, release interferon (IFN)-gamma into the supernatant when immunized with picryl chloride epicutaneously and then exposed to antigen (haptenized cells) in vitro 4 days later. The failure in IFN-gamma production maps to the major histocompatibility complex (MHC; H-2d) in the congenic BALB/c, BALB/k and BALB/b mice. The evidence that this is an MHC regulation of the class of response to a range of antigens and not a classical Ir gene effect is (a) the difference is seen with several antigens including picryl chloride, "oxazolone" and purified protein derivative of tuberculin and (b) BALB/c mice, which fail to produce IFN-gamma, show excellent contact sensitivity to picryl chloride. It was also found that the crosses between responder and nonresponder strains (CBA x BALB/c)F1 respond to antigen on responder cell but not on nonresponder cells. This influence of MHC on the class of the immune response is a possible basis for some of the associations of MHC with disease.

Experimental myasthenia gravis in congenic mice. Sequence mapping and H‐2 restriction of T helper epitopes on the α subunits of Torpedo californica and murine acetylcholine receptors

“…It may be related instead to the antibody repertoire, possibly influenced by the Th repertoire. The MHC haplotype may influence the immune response to antigens also in manners other than restriction of antigen presentation, as it was found that the H-2d haplotype correlates with poor IFN-y response to several antigens [41]. This may explain the relative resistance of BALB/c mice to autoimmune syndromes, including EAMG.…”

“…It is curious that strongly autoreactive Th cells are present in H-2d strains, which have less propensity than the H-2b strains to develop EAMG [7]. Various considerations may reconcile this paradox, including the fact that myasthenic symptoms are ultimately due to anti-TAChR antibodies cross-reacting with mouse AChR [ 11, whose production may not need autoreactive Th cells, and, in the BALB/c mice, the described poor ability of this strain to secrete I F N y [41]. Finally, highly susceptible strains, like C57BL/6, may develop AChR-specific cytotoxicity, which may play a role in determination of severe EAMG.…”

Genetic architecture of tuberculosis resistance in a mouse model of infection

“…31,32 In mice, different alleles at specific H-2 loci affected survival after i.v. infection with virulent MTB, the level of delayed type hypersensitivity (DTH), T cell proliferative response to mycobacterial antigens, and efficacy of antituberculosis vaccination with live attenuated Mycobacterium bovis (BCG), 31 production of IFN-g by mycobacteria-specific T cells, 33,34 as well as production of mycobacteria-specific antibodies. 9,26 Mouse MHC complex contains several genes that participate in processing and presentation of antigenic peptides to cytokine-producing and cytotoxic T cells.…”

Major histocompatibility complex regulation of interleukin‐5 production in the mouse

“…In the course of these studies it was found that CBA mice immunized with PCI or Ox make IFNy when their immune cells are exposed to the specific antigen in vitro, whereas BALBk immune cells failed to make IFNy [6].…”

“…MHC influence on IFN-y production was formally demonstrated using congenic BALBk (H-2d) BALB/k (H-2k) and BALB/b (H-2b) mice [6]. Initially, we interpreted the phenomenon of MHC influence on IFNy production as the [I 116131 Immunoglobulin A ability of antigen to activateTH1-like cells in H-2k mice and TH2-like cells in H-2d mice, and to support this assumption, we analyzed the production of a TH2-derived lymphokine, IL-5, in H-2k and H-2d mice.…”