EXPRESSION OF IR GENES IN T CELLS

1978 ◽  
pp. 529-537 ◽  
Author(s):  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
Jacques Thèze ◽  
Baruj Benacerraf
Keyword(s):  
T Cells ◽  
Ir Genes

scholarly journals ALLOANTISERUM-INDUCED INHIBITION OF IMMUNE RESPONSE GENE PRODUCT FUNCTION

1974 ◽  
Vol 139 (3) ◽  
pp. 679-695 ◽  
Author(s):  
Ethan M. Shevach ◽  
Ira Green ◽  
William E. Paul
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Lymphocytes ◽  
Cell Surface ◽  
Glutamic Acid ◽  
Gene Product ◽  
Lymphoid Cells ◽  
Immune Response Gene ◽  
Ga Response ◽  
Ir Genes

It has been previously demonstrated that alloantisera can specifically block the activation of T lymphocytes by antigens, the response to which is linked to the presence of histocompatibility (H) types against which the alloantisera are directed. Thus, strain 13 anti-2 serum can inhibit the activation of (2 x 13)F1 T lymphocytes by a DNP derivative of a copolymer of L-glutamic acid and L-lysine (DNP-GL), an antigen the response to which is controlled by a 2-linked Ir gene. It was proposed that alloantisera can inhibit T-lymphocyte antigen recognition through interference with the activity of immune response (Ir) gene products. In order to further study whether the inhibitory antibodies within the alloantisera are directed against H antigens or against the products of the Ir genes, we have examined whether the anti-2 serum can inhibit the function of an Ir gene (the L-glutamic acid and L-alanine [GA] gene), which is normally linked to strain 2 H genes when this gene occurs in an outbred animal lacking strain 2 H genes. In the majority of cases, the anti-2 serum was capable of inhibiting the in vitro proliferative response to GA of T cells derived from animals that were GA+2+, but the serum had little if any effect on the GA response of T cells from GA+2- animals. Furthermore, an antiserum prepared in strain 13 animals against the lymphoid cells of a GA+2- outbred animal was devoid of inhibitory activity on the GA response of cells from a (2 x 13)F1, while an antiserum prepared in strain 13 animals against the lymphoid cells of a GA+2+ outbred animal was capable of specifically inhibiting the response to GA. It thus appears that the inhibition of the GA response by the anti-2 serum is primarily mediated via antibodies directed toward strain 2 H antigens rather than antibodies specific for the product of the GA Ir gene. The mechanism of alloantiserum induced suppression of Ir gene function would then be by steric interference with the Ir gene product on the cell surface, rather than by direct binding to it. This conclusion implies that the products of both the H genes and the Ir genes are physically related on the cell surface. The implications of such a relationship in terms of the fluid-mosaic model of the lymphocyte surface are discussed.

scholarly journals GRAFT-VERSUS-HOST REACTION ACROSS DIFFERENT REGIONS OF THE H-2 COMPLEX OF THE MOUSE

1973 ◽  
Vol 137 (5) ◽  
pp. 1213-1225 ◽  
Author(s):  
Jan Klein ◽  
Jong M. Park
Keyword(s):  
T Cells ◽  
Mixed Lymphocyte Reaction ◽  
Graft Versus Host Reaction ◽  
Spleen Cells ◽  
Host Reaction ◽  
Graft Versus Host ◽  
D Region ◽  
The Individual ◽  
Ir Genes

H-2 crossovers and their parental strains were arranged into 35 combinations in which the adult donor of spleen cells differed from the newborn recipient in the whole H-2 complex, or in three, two, or one region of the complex. A Simonsen splenomegaly assay was then used to test the contribution of the individual H-2 regions to the graft-versus-host reaction (GVHR). It was shown that the strongest GVHR was associated with the Ir region. Differences in the Ir region caused significant splenomegaly in spite of the fact that no antigens detectable by conventional serological methods have thus far been associated with this region. Differences in the K and D regions showed only a borderline effect on GVHR in spite of the fact that these regions code for most, if not all, of the antigens detectable by conventional serological and transplantation methods. The K region alone caused no stronger GVHR than the D legion alone; however, K + Ir region differences led to much stronger GVHR than D region differences. The Ss-Slp region also showed only a borderline effect on GVHR. Differences in two or more H-2 regions usually caused greater splenomegaly than differences in each of the regions separately. On the basis of these findings it is concluded that the strongest GVHR is caused by genes distinct from the known histocompatibility genes of the H-2 complex. It is speculated that the GVHR genes are identical with the mixed lymphocyte reaction (MLR) and Ir genes and that the product of these genes are receptors on the surface of the thymus-derived lymphocytes (T cells).

scholarly journals The role of H-2-linked genes in helper T-cell function. VI. Expression of Ir genes by helper T cells.

1979 ◽  
Vol 149 (3) ◽  
pp. 780-785 ◽  
Author(s):  
P Marrack ◽  
J W Kappler
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cell Function ◽  
High Responder ◽  
Helper T Cells ◽  
Gene Products ◽  
Low Responder ◽  
Sites Of Action ◽  
Ir Genes

We examined the expression of (TG)-A--L specific Ir genes in helper T cells using T cells from low responder leads to (B10, high responder x low responder) F1 chimeric mice. In this paper, the low responder strain studied was B10.M, H-2f. B10.M T cells from these chimeric animals do not help anti-TNP-(TG)-A--L responses, even though they have matured in a high responder thymus and been primed and challenged with antigen on high responder Mphi and B cells. These findings indicate that in the H-2f haplotype an Ir-gene controlling anti-(TG)-A--L activity is expressed in helper T cells. The findings are in contrast to those we have obtained and previously reported with T cells of another low responder haplotype, H-2a. Taken together with our previous findings that (TG)-A--L specific Ir genes are expressed by B cells and Mphi of both the H-2a and H-2f haplotypes, the results indicate two sites of action for Ir genes, and suggest two different gene products acting at different stages of the response, both of which are defective in H-2f cells, and only one of which is defective in H-2a cells.

scholarly journals Genetic control of the immune response to myoglobins. Both low and high responder T cells tolerant to the other major histocompatibility complex help high but not low responder B cells

1982 ◽  
Vol 156 (3) ◽  
pp. 791-809 ◽  
Author(s):  
Y Kohno ◽  
JA Berzofsky
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
High Responder ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Cell Repertoire ◽  
Helper Activity ◽  
Low Responder ◽  
Ir Genes

We sought to examine the role of immune response (Ir) genes in helper T cells. To eliminate allogeneic effects, we used neonatally tolerized mice. The results bear not only on the mechanism of Ir genes, but also on the development of the T cell repertoire. B 10.BR (H-2(k)) or C57BL/10 (H-2(b)) mice, which were low responders to myoglobin (Mb), were neonatally tolerized to high responder H-2(d) alloantigens, and B10.D2 mice, which were high responders to Mb, were neonatally tolerized to low responder H-2(k) or H-2(b) alloantigens. Spleen cells from these tolerized mice did not show any reactivity in mixed-lymphocyte reaction or cell-mediated lympholysis against alloantigens used in tolerization. Mb-immune F(1) B cells were helped comparably by Mb-immune tolerized low or high responder T cells. Thus, low responder T cells functioned equivalently to high responder T cells. The failure of nonimmune T cells from tolerized low responder mice to help F(1) B cells and antigen-presenting cells (APC) indicated that collaboration between B10.BR or C57BL/10 T cells and F(1) B cells was not caused by a positive allogeneic effect. Spleen cells from tolerized mice were contaminated with 2-4 percent chimeric F(1) cells, as judged by fluorescence-activated cell sorter analysis, and no F(1) alloantigens were detectable in the thymus. However, removal of chimeric F(1) T cells from the tolerized cell population by treatment with anti-H-2 and complement did not change the helper activity of tolerized low responder T cells. These data indicated that helper activity in the T cell population from low responder mice was not due to F(1) cells. Also, the level of contamination was not sufficient to quantitatively account for the help. In examining the genetic restriction of these tolerized T cells, we found that T cells from tolerized low responder B10.BR or C57BL/10 mice helped F(1) or high responder B10.D2 B cells and APC but not syngeneic B10.BR or C57BL/10 B cells and APC, which were immunized with Mb-coupled fowl gamma globulin instead of Mb to prime low responder B cells with Mb. On the other hand, high responder B 10.D2 tolerized T cells helped syngeneic B 10.D2 B cells but not allogeneic low responder B10.BR B cells. These data indicated that clones of helper T cells specific for Mb exist in low responder mice, and these are not phenotypically different from those in high responder mice, in that both help high responder and F(1) but not low responder B cells and APC. These data are discussed in terms of the mechanism for Ir gene control, and the mechanism of T cell repertoire development- whether intra- or extrathymically-in neonatally tolerized mice.

scholarly journals Antiidiotype stimulation of antigen-specific antigen-independent antibody responses in vitro. I. Evidence for stimulation of helper T lymphocyte function.

1983 ◽  
Vol 158 (2) ◽  
pp. 465-476 ◽  
Author(s):  
H Z Weissberger ◽  
R R Shenk ◽  
H B Dickler
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Specific Antigen ◽  
Lymphocyte Function ◽  
Accessory Cells ◽  
Helper Function ◽  
Ir Genes ◽  
Stimulation Of

Antibodies specific for the idiotypes of B10 anti-(T,G)-A-L antibodies (anti-Id) induced in vivo (T,G)-A-L-primed lymphocytes to secrete anti-(T,G)-A-L antibodies in vitro in the absence of antigen. Responses to anti-Id were quantitatively and qualitatively similar to responses to antigen. Responses were specific in that: (a) only lymphocytes primed in vivo with (T,G)-A-L (but not other antigens or unprimed cells) were inducible; (b) only anti-Id (but not a variety of control antibodies) induced responses; and (c) only anti-(T,G)-A-L antibodies were secreted. Antigen-primed T lymphocytes mixed with unprimed B plus accessory cells also responded to anti-Id and the phenotype of the responding T cells was Lyt-1+, Lyt-2-. Supernatants obtained from antigen-primed T cells incubated for 3 d with anti-Id (but not when incubated with controls) provided help to unprimed B plus accessory cells in the presence of anti-Id, thus providing direct evidence for induction of T lymphocyte helper function by anti-Id. In contrast to responses to (T,G)-A-L, responses to anti-Id did not appear to be regulated by H-2-linked Ir genes. The system described is a powerful tool for delineation of the mechanisms whereby antiidiotype antibodies affect lymphocyte function.

scholarly journals Antigen-specific helper T cells required for dominant production of an idiotype (THId) are not under immune response (Ir) gene control.

1980 ◽  
Vol 152 (6) ◽  
pp. 1571-1582 ◽  
Author(s):  
K Bottomly ◽  
P H Maurer
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Helper T Cells ◽  
Gene Control ◽  
Gene Products ◽  
Histocompatibility Complex ◽  
Normal Carrier ◽  
Carrier Molecule ◽  
Ir Genes

Responder and nonresponder mice primed with poly-(L-glutamic acid,L-lysine,L-phenylalanine) (GLPhe), the response to which is under the control of immune response (Ir) genes, were used as a source of both types of helper T cells required for a T15 idiotype dominated T-dependent anti-phosphorylcholine (PC) response. It was found that the activity of one of the helper T cells needed for an anti-PC response was under major histocompatibility complex (MHC)-linked Ir gene control, and only GLPhe-primed responder mice could be used as a source of these cells. These T cells (ThMHC) whose presence is required for in vivo T-B collaboration are found in normal and anti-mu-treated mice, and their activity depends on the hapten being physically linked to the carrier molecule. By contrast, the activity of the second helper T cell (ThId) required for a T15-dominated anti-PC response was present in both GLPhe-primed responder and nonresponder mice. The ThId cell set that is missing or deficient in anti-mu treated mice can be restored by the addition of T cells from normal, carrier-primed donors and restimulating with the priming carrier. When T cells from GLPhe-primed donors are used as a source of ThId cells, both responder and nonresponder donors provide helper cells capable of inducing syngeneic B cells to produce a T15 dominated anti-Pc response. These results are interpreted to suggest that idiotype recognizing helper T cells (ThId) recognize antigen independent of known Ir gene products.

scholarly journals Ir-genes in H-2 regulate generation of anti-viral cytotoxic T cells. Mapping to K or D and dominance of unresponsiveness.

1978 ◽  
Vol 148 (2) ◽  
pp. 592-606 ◽  
Author(s):  
R M Zinkernagel ◽  
A Althage ◽  
S Cooper ◽  
G Kreeb ◽  
P A Klein ◽  
...  
Keyword(s):  
T Cells ◽  
Cytotoxic T Cells ◽  
Cytotoxic T Cell ◽  
Mouse Strains ◽  
Self Tolerance ◽  
Allele Specific ◽  
Low Responder ◽  
Cytotoxic T Cell Responses ◽  
Ir Genes

H-2 dependent and virus-specific Ir genes regulate the generation of primary virus-specific K or D restricted cytotoxic T-cell responses in vivo. The following examples have been analyzed in some detail: first, Dk restricted responses to vaccinia in Sendai viruses are at least 30 times lower than the corresponding K-restricted responses irrespective of the H-2 haplotypes (k, b, d, dxs, dxq) of K and I regions; in contrast, LCMV infection generates high responses to Dk. These findings are consistent with but do not prove that this Ir gene maps to D. Second, Db restricted responses to vaccinia and Sendai viruses are high in strains possessing the Kq or KbIb, KbaIb haplotype, are very low in strains with Kk, and relatively low in mouse strains of the KdI-Ad haplotype; LCMV generates high Db restricted response in the presence of Kk. This Ir gene for the response to vaccinia and Sendai viruses maps to K since B10.BYR (KqIkdDb) is a responder and B10.A (2R) is a nonresponder (KkIkdDb). Third, virus and K or D allele specific nonresponsiveness is dominant with variable penetrance; in heterozygous mice the nonresponder Kk allele over-rides responsiveness normally found in KbDb or KqDb combinations. Fourth, when (responder X nonresponder)F1 lymphocytes are stimulated in an environment expressing vaccinia virus plus only a high responder Kb or Kq allelle and Db, response to vaccinia Db is high; in contrast when the same F1 cells are stimulated in an environment expressing the low responder allele Kk, response to vaccinia Db is low. Thus absence of Kk during immunization allows generation of high responsive Db restricted vaccinia specific cytotoxic T cells. The Dk dependent low response to vaccinia Dk can be explained by a preclusion rule or by failure of vaccinia to complex with Db; however the analysis of Kk dependent low response to vaccinia Db does not support these explanations or that self-tolerance is responsible for this Ir effect but is compatible with the interpretation that Kk vaccinia is immunodominant over Db vaccinia. These results are discussed with respect to (a) possible mechanisms of regulation by Ir genes and (b) H-2 polymorphism and HLA-disease association.

scholarly journals Distinct Ir genes for helper and killer cells in the cytotoxic response to H-Y antigen.

1979 ◽  
Vol 150 (5) ◽  
pp. 1134-1142 ◽  
Author(s):  
H von Boehmer ◽  
W Haas
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Ctl Response ◽  
Helper Cells ◽  
Bone Marrow Chimeras ◽  
Ir Genes

The H-Y-specific cytotoxic T-cell response requires helper cells: cells from bone marrow chimeras B6 X CBA leads to B6, B6 X CBA leads to B10.A (5R), or B6 X CBA leads to CBA are each unable to respond to H-2k male cells. If, however, cells from B6 X CBA leads to B6 or B6 X CBA leads to B10.A (5R) chimeras are adoptively transferred together with cells from B6 X CBA leads to CBA chimeras, H-Y-specific CTL restricted to H-2k can be obtained. Thus, cells from B6 X CBA leads to B6 or B6 X CBA leads to B10.,A (5R) chimeras (restricted to the left end of the H-2b haplotype) can help CTL precursors from B6 X CBA leads to CBA chimeras (restricted to H-2k). The two classes of T cells required for the CTL response to H-Y antigen are controlled by different IR genes. All H-Y-specific CTL obtained from chimeras B6 + CBA leads to B6 X CBA were found to be of B6 origin. This suggests that CTL or their precursors must express antigens encoded in the left end of the H-2b haplotype for interaction with helper cells.

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