Genetic control of specific immune suppression. II. H-2-linked dominant genetic control of immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT).

Self Cite

The helper and suppressor regulatory activities exerted on antibody responses by T lymphocytes are associated with subregions of the I region of the murine H.2 (major histocompatibility) complex. Using antisera defining Ia antigens, raised by immunization between congenic pairs of mice differing at the ! region, specific suppressor T cells (1, 2) and their soluble and mediators (3-5)have been shown to bear I-J subregion coded determinants, whereas certain helper (enhancing) factors and possibly helper cells possess I-A coded determinants (6, 7).i Analysis of the effects of such specific anti-Ia antisera on immune responses can, therefore, provide information concerning the regulatory functions of the various ! region products, This approach has been used in various model systems, and several investigators have reported marked inhibition of in vitro lymphocyte reactivity by distinct anti-la antisera (8-12). It was thus appropriate to determine whether such antisera would also alter in vivo immune responses. We reported recently (13) that microliter amounts of alloantisera against I k and I # gene products were able to potentiate primary IgM and IgG in vivo plaque-forming cell (PFC) 2 responses to suboptimal immunogenic doses of sheep erythrocytes (SRBC) in A/J and BALB/c mice, respectively. The same immunopotentiating activity was observed with an anti-I-J k antiserum in A/J mice. Further studies revealed that in vivo administration of the same anti-I-J k antiserum decreases tumor growth in A/J mice inoculated with a syngeneic methylcholanthrene-induced fibrosarcoma (14), known to elicit potent suppressor T-cell responses active in inhibiting antitumor immunity (15, 16). These observations raised the possibility that the potentiation of SRBC PFC responses observed with the anti-I-J k antiserum, *

mentioning

confidence: 87%

In vivo effects of anti-Ia alloantisera. I. Elimination of specific suppression by in vivo administration of antisera specific for I-J controlled determinants.

Pierres¹,

Germain²,

Dorf³

et al. 1978

Self Cite

“…In SJL nonresponder mice, GT-induced suppressor ceils are able to suppress both GT-MBSA and GAT-MBSA responses (21). GT and GAT, however, are highly cross-reactive at the antibody level.…”

Section: Discussionmentioning

confidence: 99%

Differential major histocompatibility complex-related activation of idiotypic suppressor T cells. Suppressor T cells cross-reactive to two distantly related lysozymes are not induced by one of them.

Adorini¹,

Harvey²,

Rozycka-Jackson³

et al. 1980

B10 (H-2b) mice are genetic nonresponders to hen egg-white lysozyme (HEL) and the distantly related human lysozyme (HUL). However, anti-HEL or anti-HUL primary antibody responses in vivo or in vitro can be obtained in B10 mice by immunization with the appropriate lysozyme coupled to erythrocytes. T cells able to suppress either anti-lysozyme plaque-forming cells (PFC) response are induced in B10 mice after immunization with HEL-complete Freund's adjuvant (CFA) or HUL-CFA. This cross-reactivity of HEL and HUL in the induction and the expression of suppressive activity is in marked contrast to their very low cross-reactivity at the PFC level. These results suggest that either HEL or HUL can stimulate a suppressor T cell which recognizes a particular epitope present on both lysozymes. Suppressor cells induced by HEL or HUL bear the same predominant idiotype found on the majority of anti-HEL antibodies, and on the small proportion of anti-HUL antibodies cross-reactive with HEL. B10.Q (H-2q) mice are responders in vivo to HEL-CFA, but not to HUL-CFA. In contrast to B10, HEL-CFA priming in B10.Q micr induces helper cells whereas HUL-CFA priming induces suppressor cells. These suppressor cells are cross-reactive with HEL and are fully able to suppress HEL-specific helper cells. The presence of HEL-specific suppressor cell precursors in B10.Q mice which are not activated by HEL, seems to implicate differential choice by the antigen presenting system as a basis for Ir gene control, rather than the absence of a regulatory cell type from the T cell repertoire.

“…The above results illustrate that homozygous H-2 k~k animals are able to respond, whereas heterozygous H-2 q~k animals are not, a finding which suggests that responsiveness is regulated either by (a) a recessive trait or (b) a dominant suppressor gene(s) which causes nonresponsiveness. This is an unusual finding in that most H-2-linked Ir genes defined to date have shown dominant responsiveness (6); however, several workers have recently demonstrated the existence of H-2 linked, dominant immune suppression gene(s) (17,18). It is, therefore, important to determine whether any H-2 heterozygous animal is capable of a cell-mediated cytotoxic response to AKR tumor cells, or whether only H-2 k~k homozygous mice are able to respond.…”

Section: Kinetics and Specificity Of The Cell-mediated Response To Akmentioning

confidence: 99%

Genetic control of cell-mediated responsiveness to an AKR tumor-associated antigen: mapping of the locus involved to the I region of the H-2 complex.

Meruelo¹,

Deak²,

McDevitt³

1977

The role of H-2-linked genes in controlling resistance to murine leukemia viruses has been studied by measuring the cell-mediated immune response of F1 hybrid mice (between AKR and various C3H and C57BL/10 derived, H-2 congenic strains) to an AKR tumor cell line, BW5147. The studies have shown that the ability to generate a primary or secondary cell-mediated response to an AKR tumor cell antigenic determinant is under H-2 linked control. The locus determining CML responsiveness maps in the I-J subregion. Nonresponsiveness is associated with the H-2q/k and H-2b/k hybrid genotypes, whereas responsiveness is associated with the H-2k/k homozygous genotype. Nonresponsiveness may result from (a) dominant suppression; (b) recessive responsiveness; or (c) an alternate mechanism not yet understood. This type of control may be one of several H-2-associated mechanisms of defense against virus-induced neoplasms.