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.

Meruelo, Daniel; Deak, Beverly D.; McDevitt, Hugh O.

doi:10.1084/jem.146.5.1367

Cited by 32 publications

(10 citation statements)

References 23 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From our experiments it cannot be established whether the MLV controlling genes are identical to some of the genes involved in these systems. As far as the H-Zassociated factors are concerned, it is known that Rgv-1 at the K end, controlling GLV (Lilly, 1971) Rfv-1 at the D end, controlling FLV (Chesebro et al, 1974), Rrv-1 and another gene of the I region, controlling the ARadLV (Lonai and Haran-Ghera, 1977) and finally a gene of the D region controlling the K-Rad LV (Meruelo et al, 1977~) are very probably different genes. Furthermore, other genes of the H-2 complex, controlling GLV (32) and possibly FLV (Chesebro, personal communication) in addition to Rgv-1 and Rfv-I, also exist.…”

Section: Discussionmentioning

confidence: 99%

Genetic control of sensitivity to moloney‐virus‐induced leukemias in mice. I. Demonstration of multigenic control

Gisselbrecht

Pozo

Debré

et al. 1978

Intl Journal of Cancer

View full text Add to dashboard Cite

The appearance of hematopoietic malignancies and the level of viremia were studied in mice of different inbred strains and their F1 or F2 hybrids inoculated with the Moloney leukemia virus (MLV) The viremia was regularly measured in individual mice by radioimmunoassay of the major internal virion component p30. A complex genetic control was found. (1) The level of circulating virus was controlled by at least two genes. An H‐2 linked gene, tentatively called Rmv‐1, displayed a dominant sensitivity. Alleles for resistance existed in H‐2b and H‐2r haplotypes and alleles for sensitivity in H‐2a, H‐2d and H‐2f. Another gene with dominant resistance mapped outside the H‐2 complex and probably interacted with Rmv‐1. (2) A good correlation existed between viremia and the appearance of leukemias, the most viremic strains being also the most leukemic. (3) Nevertheless, additional genes which were not involved in the viremia control could be determinant in the induction of malignancies. One of them with a resistant allele in DBA/2 mice seemed to inhibit the appearance of leukemia despite a high level of viremia. Another gene controlled the spleen involvement resulting in generalized leukemias in sensitive lines contrasting with mainly thymus‐localized tumors in resistant animals.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic control of sensitivity to moloney‐virus‐induced leukemias in mice. I. Demonstration of multigenic control

Gisselbrecht

Pozo

Debré

et al. 1978

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Cells were prepared and cell-mediated lympholysis activity measured as previously described (6), except that cells used for this test were grown in RPMI-1640 with 25 mM Hepes (Grand Island Biological Co., Grand Island, N. Y.).…”

Section: Preparation Of Effector Cells '~Cr-labeled Target Cells Anmentioning

confidence: 99%

A role for elevated H-2 antigen expression in resistance to neoplasia caused by radiation-induced leukemia virus. Enhancement of effective tumor surveillance by killer lymphocytes.

Meruelo¹

1979

The Journal of Experimental Medicine

Self Cite

View full text Add to dashboard Cite

Resistance to neoplasia caused by radiation-induced leukemia virus (RadLV) is mediated by gene(s) in the H-2D region of the major histocompatibility complex. The previous observation that rapid increases in cellular synthesis and cell-surface expression of H-2 antigens are detectable immediately after virus inoculation has suggested that altered expression of H-2 antigens may play a significant role in the mechanism(s) of host defense to virus infection. This concept is supported by the following observations. First, cell-mediated immunity against RadLV transformed or infected cells can be detected with ease when H-2-positive target cells are used in the cell-mediated lympholysis (CML) assay. (Although RadLV transformed cells obtained from overtly leukemic animals and maintained in tissue culture are H-2 negative, these cells can regain their H-2 phenotype by in vivo passage in normal animals. The H-2-negative cells are poor targets in a CML assay.) Second, resistant mice develop greater numbers of effectors when infected with RadLV than do susceptible mice. Third, injection of normal (uninfected) thymocytes into syngeneic recipients of resistant or susceptible H-2 type does not stimulate a CML response. However, injection of RadLV infected thymocytes from resistant mice produces a vigorous CMI response, and such thymocytes elicit the strongest response at a time when both H-2 and viral antigen expression is elevated. By contrast, injection of infected thymocytes from susceptible mice, which express viral antigens, but low levels of H-2 antigens, does not stimulate a CML reaction. These findings may explain the easier induction of leukemia found by many investigators when virus is inoculated into neonatal mice and the preferential thymus tropism of some oncogenic type-C RNA virus. Cells expressing very low levels of H-2, such as thymocytes, may serve as permissive targets for virus infection because they lack an important component (H-2 antigens) of the dual or altered recognition signal required to trigger a defensive host immune response.

show abstract

“…[341 Tada et al [57] Th+ze et al [62] Greene et al [15] Meruelo et al [28] the I-J subregion are also associated with soluble factors which suppress IgG responses to haptens coupled to the carrier keyhole limpet hemacyanin (KLH)o Studies in this latter system reveal that I-J controlled determinants are codominantly expressed.…”

Section: Ill Definition Of the I-j Subregionmentioning

confidence: 99%

The I-J subregion of the murine H-2 gene complex

Murphy

1978

Springer Semin Immunopathol

View full text Add to dashboard Cite

l. OverviewIa loci, mapping in the I region of the murine H-2 gene complex, control surface determinants expressed on cells (T lymphocytes, B lymphocytes, and macrophages) which are intimately involved in the regulation and generation of cellular and humoral immunity. In the past year, a new I region locus, which controls determinants present on T lymphocytes that suppress antibody production, has been identified. This locus, Ia-4, marks a segment of chromosome, designated the I-J subregion. Studies of the I-J subregion have provided fresh insights into the genetic organization of the I region, and have advanced our understanding of the role I region loci play in the generation of immune responses.Until recently, the available data suggested that the same Ia loci are expressed in T and B lymphocytes. Studies of the Ia-4 locus reveal that Ia-4 determinants are present on suppressor T lymphocytes, but not B lymphocytes or T lymphocytes that facilitate antibody production by B lymphocytes (helper T lymphocytes). In contrast, the latter two lymphocyte populations bear determinants controlled by other loci mapping in the I region. Thus, the I region is comprised of a cluster of loci which are selectively expressed in functionally distinct lymphocyte populations.Selective expression of loci in the genome allows genetically identical cells to perform different functions. A fundamental question which must therefore be addressed is whether I region products actually play a role in the functions mediated by immunocompetent cells. The demonstration that T cell derived soluble factors which suppress humoral and cellular immunity bear I-J determinants strongly suggests an active role for these determinants in suppression.Studies with I-J bearing suppressor factors also provide further clues to the cellular interactions leading to suppression. Factor produced by one T cell subpopulation binds to and activates a second T cell subpopulation. This second T cell population either becomes the effector cell mediating suppression or regulates suppressor activity by other T lymphocytes. Although the evidence is still too fragmentary to allow clear definition of the precise role of I-J determinants, the data are consistent with their being part of the regulatory language used for communication among responding lymphocytes.0344-4325/78/0001/0111/$ 04.20

show abstract

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.

Cited by 32 publications

References 23 publications

Genetic control of sensitivity to moloney‐virus‐induced leukemias in mice. I. Demonstration of multigenic control

Genetic control of sensitivity to moloney‐virus‐induced leukemias in mice. I. Demonstration of multigenic control

A role for elevated H-2 antigen expression in resistance to neoplasia caused by radiation-induced leukemia virus. Enhancement of effective tumor surveillance by killer lymphocytes.

The I-J subregion of the murine H-2 gene complex

Contact Info

Product

Resources

About