scholarly journals Antigen-presenting cells from nonresponder strain 2 guinea pigs are fully competent to present bovine insulin B chain to responder strain 13 T cells. Evidence against a determinant selection model and in favor of a clonal deletion model of immune response gene function.

1983 ◽  
Vol 157 (4) ◽  
pp. 1287-1299 ◽  
Author(s):  
G A Dos Reis ◽  
E M Shevach
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Gene Function ◽  
Guinea Pigs ◽  
Bovine Insulin ◽  
Immune Response Gene ◽  
Cell Repertoire ◽  
Clonal Deletion ◽  
Response Gene ◽  
Selection Hypothesis

To test directly the determinant selection hypothesis of immune response gene function, we primed strain 13 T lymphocytes in vitro with allogeneic bovine insulin pulsed strain 2 macrophages. Strain 2 macrophages were found to be fully competent to present bovine insulin B chain to strain 13 T cells despite the fact that strain 2 guinea pigs are normally totally unresponsive to this antigen. These results are incompatible with a strict interpretation of the determinant selection hypothesis, which would have predicted that strain 2 macrophages would have been restricted to the presentation of A chain loop determinants. In addition, a comparison of the reactivity profiles of self-Ia- and allo-Ia-restricted strain 13 T cells to a series of synthetic B chain peptide fragments revealed that the allo-Ia-restricted populations could be activated by autologous guinea pig insulin. Taken together, these observations strongly suggest that the clonal deletion of self-reactive cells is likely to be I region restricted and that nonresponsiveness to any protein antigen may result from a restriction in the T cell repertoire that is generated during ontogeny by a clonal deletion mechanism of tolerance to self.

Determinant Selection vs Clonal Deletion Models of Immune Response Gene Function

Ir Genes ◽  
1983 ◽  
pp. 251-261
Author(s):  
George A. Dos Reis ◽  
Robert B. Clark ◽  
Ethan M. Shevach
Keyword(s):  
Immune Response ◽  
Gene Function ◽  
Immune Response Gene ◽  
Clonal Deletion ◽  
Response Gene

scholarly journals B lymphocyte immune response gene phenotype is genetically determined.

1982 ◽  
Vol 155 (4) ◽  
pp. 1239-1244
Author(s):  
H Y Tse ◽  
J J Mond ◽  
D L Longo
Keyword(s):  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Gene Function ◽  
B Lymphocyte ◽  
Immune Response Gene ◽  
Cell Immune Response ◽  
Response Gene ◽  
Genetically Determined

We examined the effects of the developmental milieu on the capacity of B cells to undergo immune response gene-controlled, T cell-dependent polyclonal proliferation. Although I-Aq poly(Glu60 Ala30 Tyr10)n (GAT)-nonresponder T cells developing in a responder environment become phenotypic GAT-responders, I-Aq B cells remain unresponsive to GAT, even after maturation in a GAT-responder animal. Conversely, (B10.A x B10.Q)F1 ([GAT responder x GAT nonresponder]F1) T cells developing in a B10.Q GAT nonresponder host fail to respond to GAT, but F1 B cells from the same F1 leads to parent chimeras make excellent proliferative responses in the presence of GAT and responder T cells. Thus, by this assay, B cell immune response gene function is genetically determined and is not affected by the developmental milieu.

scholarly journals In vitro correlate for a clonal deletion mechanism of immune response gene-controlled nonresponsiveness.

1983 ◽  
Vol 157 (3) ◽  
pp. 998-1005 ◽  
Author(s):  
N Ishii ◽  
Z A Nagy ◽  
J Klein
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Response Gene ◽  
Mouse Strains ◽  
Single Chain ◽  
Cell Repertoire ◽  
Clonal Deletion ◽  
Class Ii Mhc ◽  
Antigen Presenting

We used T cell-antigen-presenting cell (APC) combinations from two pairs of recombinant mouse strains, B10.A(4R)-B10.A(2R) and B10.S(7R)-B10.S(9R) (abbreviated 4R, 2R, 7R, 9R, respectively), which differ from each other only in the nonexpression vs. expression of cell-surface E molecules, to study the mechanism of the Ir gene-controlled (E-restricted) response to the terpolymer poly(glu51lys34tyr15) (GLT). No response to GLT occurred when the APC were from E-nonexpressor strains 4R and 7R. When APC from E-expressor strains were used and alloreactivity against the incompatible E molecules was removed by BUdR + light treatment, 7R T cells responded to GLT presented by 9R APC, but 4R T cells failed to respond to GLT presented by 2R APC. However, 4R T cells mounted a proliferative response to GLT presented by fully allogeneic 5R or 9R APC. The latter response was completely abolished by the depletion of cells alloreactive against 2R and 5R or 2R and 9R. Since removal of alloreactivity against 5R plus 9R did not affect the response of 4R T cells to GLT presented by either 5R or 9R cells, we conclude that the 4R T cells generated in response to GLT cross-react with the additional incompatibility presented by 2R cells, that is, the Ek beta chain. In contrast, 7R T cells recognizing GLT presented by 9R APC do not cross-react with Ek beta. These results demonstrate that "blind spots" in the T cell repertoire produced by depletion of cells alloreactive against a single chain of a class II MHC molecule can render a strain nonresponsive to a synthetic polypeptide antigen, and that this nonresponsiveness corresponds to that attributed to the MHC-linked Ir genes.

scholarly journals HISTOCOMPATIBILITY TYPE AND IMMUNE RESPONSIVENESS IN RANDOM BRED HARTLEY STRAIN GUINEA PIGS

1970 ◽  
Vol 132 (6) ◽  
pp. 1259-1266 ◽  
Author(s):  
William John Martin ◽  
Leonard Ellman ◽  
Ira Green ◽  
Baruj Benacerraf
Keyword(s):  
Immune Response ◽  
Inbred Strain ◽  
Guinea Pigs ◽  
Histocompatibility Antigen ◽  
Specific Immune Response ◽  
Immune Response Gene ◽  
Immune Responsiveness ◽  
Major Histocompatibility ◽  
Response Gene ◽  
Major Histocompatibility Antigen

Outbred Hartley strain guinea pigs capable of responding immunologically to 2,4-dinitrophenylated poly-L-lysine were shown to display a histocompatibility specificity in common with inbred strain 2 guinea pigs. This histocompatibility specificity was not detected in guinea pigs unable to respond immunologically to DNP-PLL. The result suggests that the poly-L-lysine specific immune response gene is very closely linked or even identical with a gene determining a major histocompatibility antigen in guinea pigs.

scholarly journals The xid gene controls Ia.W39-associated immune response gene function.

1981 ◽  
Vol 153 (5) ◽  
pp. 1113-1123 ◽  
Author(s):  
L J Rosenwasser ◽  
B T Huber
Keyword(s):  
Immune Response ◽  
Gene Function ◽  
Immune Response Gene ◽  
T Cell Proliferation ◽  
Response Gene ◽  
Histocompatibility Complex ◽  
Ia Antigens ◽  
Antigen Presenting ◽  
Ir Genes

Immune response (Ir) genes are encoded for by the I region of the major histocompatibility complex (MHC). A class of serologically defined specificities, Ia antigens, is also encoded for by genes within this region. A new Ia specificity, Ia.W39, has recently been defined. It is private for I-Ab and its expression is controlled by a gene on the X-chromosome. Using different approaches, the role of Ia.W39 in the immune response of H-2b mice to beef insulin was examined in a macrophage-dependent T cell proliferation assay. It was found that beef insulin-related Ir gene function was associated with the expression of Ia.W39 by antigen-presenting macrophages and that control of this Ir gene function was X-linked (xid gene).

DETERMINANT SELECTION: A MACROPHAGE-MEDIATED IMMUNE RESPONSE GENE FUNCTION

1978 ◽  
pp. 405-415 ◽  
Author(s):  
Alan S. Rosenthal ◽  
Lanny J. Rosenwasser ◽  
Marcello A. Barcinski
Keyword(s):  
Immune Response ◽  
Gene Function ◽  
Immune Response Gene ◽  
Response Gene

Thymic immune response gene function in radiation chimeras reconstituted with purified hemopoietic stem cells

1987 ◽  
Vol 17 (4) ◽  
pp. 471-475 ◽  
Author(s):  
W. Martin Kast ◽  
Arie C. Voordouw ◽  
Tine Leupers ◽  
Jan W. M. Visser ◽  
Cornelis J. M. Melief
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Gene Function ◽  
Immune Response Gene ◽  
Hemopoietic Stem Cells ◽  
Response Gene ◽  
Radiation Chimeras

scholarly journals Generation of T cell colonies from responder strain 2 guinea pigs that recognize the copolymer L-glutamic acid, L-lysine in association with nonresponder strain 13 Ia antigens.

1982 ◽  
Vol 155 (2) ◽  
pp. 635-640 ◽  
Author(s):  
R B Clark ◽  
E M Shevach
Keyword(s):  
T Cells ◽  
Glutamic Acid ◽  
Gene Function ◽  
Guinea Pigs ◽  
Liquid Culture ◽  
Soft Agar ◽  
Clonal Deletion ◽  
Alloreactive T Cells ◽  
Ia Antigens

T cells from nonimmune responder strain 2 guinea pigs were primed in vitro to the copolymer GL in association with allogeneic, nonresponder strain 13 PEC. T cells that recognized GL in association with strain 13 Ia were separated from alloreactive T cells by cloning the population in soft agar following the priming in liquid culture. The existence of T cells of responder origin that recognize antigen in association with nonresponder macrophages is most consistent with clonal deletion models of Ir gene function.

Sign in / Sign up

Export Citation Format

Share Document