The research will continue to employ synthetic polymers of amino acids (T cell dependent and major histocompatibility-complex linked) to study aspects of genetic control of the immune response (lr) in mice. Wild mice (B10.W) having known la antigens, and H-2bm12 mice with mutations lA will be immunized with H-2b linked immunogens to determine the association of lr and known la antigens; i.e. lr=la? Anti-lD against the polymers GLPhe, GPhe, GAPhe, GLA40 and some sequential polymers will be studied to determine a) whether the anti polymer idiotypic determinants (VH region?) from mice within a murine strain as well as with different strains might be conserved and if so the extent of it and b) the possible importance of the association of the lD determinants in anti-GPhe with H2q. The biological activities of the various anti-lD as they effect both B cell i.e. PFC responses, and T cell functions i.e. proliferative responses: will be investigated. The anti-lD will be used to determine the nature of the ID determinants on suppressor, or helper T cells: or """"""""factors"""""""" from responder and non-responder mice. The characterization of antigen specific T cell receptors (GLA40 system) will continue and will include determining the possible association of lD and la determinants with """"""""the receptor."""""""" Our present success in the production of rabbit anti-lD sera against GLA40 and the production of hybridomas (monoclonal) against GLA40 are important for receptor work. In order to obtain significant amounts of T cells for isolation of receptors, we are developing techniques for T cell cloning and hybridization. The following systems of indicated H-2 will be studied to determine the number of unique T cell lines that may be produced and separated, and the antigen presenting cell haplotype specificities that may be involved. The l-GLPhe9:a) Fl(H-2f x H-2s) responding to GLPhe9 and GLT, b) Fl(H-2d x H-2s) responding to GLPhe9, GLT and GPhe, c) Fl(H-2d x H-2q) responding to GLPhe9, GLT and GPhe, d) H-2q responding to GLT and GPhe. The 2-GLT15: Fl(H-2f x H-2s) responding to GLT15 and GLPhe. The 3-GPhe: Fl(H-2d x H-2s). Sufficient amounts of antibody are being prepared against some of the sequential polymers so that anti-lD sera can be raised and the lD determinants characterized and compared within a single respnding haplotype congenic mice or from 2 different responding haplotypes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI007825-20
Application #
3124391
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1978-01-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
20
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Liu, D C; Grun, J L; Maurer, P H (1991) Differential effects of poly (Glu60, Phe40) (GPhe) on murine TH1 and TH2 cells. Cell Immunol 133:420-33
Grun, J L; Liu, D C; Maurer, P H (1990) Enhanced proliferation of murine T cell lines following interaction of poly(Glu60,Phe40) (GPhe) and antigen-presenting accessory cells. II. The role of accessory cells and cytokines in the activity of GPhe on antigen-independent proliferation. Cell Immunol 129:213-27
Liu, D C; Grun, J L; Maurer, P H (1990) Enhanced proliferation of murine T cell lines following interaction of poly(Glu60,Phe40) (GPhe) and antigen-presenting accessory cells. I. GPhe-stimulated enhancement of antigen-dependent proliferative responses. Cell Immunol 129:199-212
Liu, D C; Grun, J L; Maurer, P H (1990) Enhanced proliferation of murine T cell lines following interaction of Poly(Glu60, Phe40) (GPhe) and antigen-presenting accessory cells. III. Possible mechanisms responsible for activity of GPhe. Cell Immunol 131:272-83
Grun, J L; Maurer, P H (1989) Different T helper cell subsets elicited in mice utilizing two different adjuvant vehicles: the role of endogenous interleukin 1 in proliferative responses. Cell Immunol 121:134-45
Grun, J L; Maurer, P H (1988) Ir gene control of mouse responses to poly(GluArgAla) and poly(ArgAla). Immunogenetics 28:61-3
Maurer, P H; Liu, D C; Grun, J L (1987) Unusual ""cytokine"" activities of the random polymer (Glu60, Phe40) in murine immune systems. Immunol Lett 16:291-6
Peck, A B; Kimura, A K (1986) Characteristics of a T lymphocyte-enhancing Ab-specific monoclonal antibody. I. Genetic specificity and preferential enhancement of allogeneic reactions. Immunogenetics 23:284-91