Human T cell activation and proliferation have been probed by monoclonal antibodies in the presence of phorbol myristate acetate (PMA). An early activation antigen (EA 1) which was expressed by medullary thymocytes but not by peripheral blood T cells was induced rapidly by PMA and synthetic diacylglycerol. In addition, CD28 (9.3) has been defined to mediate an activation pathway. In this proposal, studies are proposed to extend these findings.
Five Aims are proposed. (1) Because of its rapid expression and the ease of detecting factors potentiating its expression, we wish to define the role of monokines in the potentiation of EA 1 expression and to identify novel monokines active on T cells. (2) To compare the activation requirements for EA 1 induction in T and B cells and to relate these findings to the expression of protein kinase C isoenzymes. (3) To clone and to express the genes encoding the major 22Kd deglycosylated peptide in the EA 1 complex so that the function of EA 1 can be studied further. (4) To further define the CD28 pathway by comparing it to the CD3/Ti pathway. (5) To ascertain whether CD28 is a receptor molecule involved in cell-cell interaction or a potential receptor for a yet to be defined cytokine. Parts of these studies will be carried out with CD28 isolated from cells. To facilitate recombinant CD28 with these studies, extracellular domains only will be generated so that sufficient amounts of CD28 are available for detailed studies. These studies will identify potential interactive surface molecules important for T cell activation. They may also provide some insights into the monocyte related activation mechanisms, some of which are defective in diseases with immunological deficiencies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA034546-07
Application #
3172265
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1982-07-01
Project End
1988-10-31
Budget Start
1988-08-01
Budget End
1988-10-31
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
Sung, S; Rose, C E; Fu, S M (2001) Intratracheal priming with ovalbumin- and ovalbumin 323-339 peptide-pulsed dendritic cells induces airway hyperresponsiveness, lung eosinophilia, goblet cell hyperplasia, and inflammation. J Immunol 166:1261-71
Kim, Y; Sung Ss; Kuziel, W A et al. (2001) Enhanced airway Th2 response after allergen challenge in mice deficient in CC chemokine receptor-2 (CCR2). J Immunol 166:5183-92
Kamochi, M; Kamochi, F; Kim, Y B et al. (1999) P-selectin and ICAM-1 mediate endotoxin-induced neutrophil recruitment and injury to the lung and liver. Am J Physiol 277:L310-9
Sung, S J; Taketomi, E A; Smith, A M et al. (1999) Efficient presentation of house dust mite allergen Der p 2 by monocyte-derived dendritic cells and the role of beta 2 integrins. Scand J Immunol 49:96-105
Smith, A M; Yamaguchi, H; Platts-Mills, T A et al. (1998) Prevalence of IgG anti-Der p 2 antibodies in children from high and low antigen exposure groups: relationship of IgG and subclass antibody responses to exposure and allergic symptoms. Clin Immunol Immunopathol 86:102-9
Sung, S S; Guo, C Y; Weed, J M (1997) Monoclonal antibodies against human dendritic cell-like peripheral blood monocytes activated by granulocyte/macrophage-colony-stimulating factor plus interleukin 4. Cell Immunol 182:113-24
Armerding, D; Hren, A; Callard, R E et al. (1996) Induction of cognate and non-cognate T-cell help for B-cell IgE production in relation to CD40 ligand expression. Int Arch Allergy Immunol 111:376-84
Bykowsky, M J; Haire, R N; Ohta, Y et al. (1996) Discordant phenotype in siblings with X-linked agammaglobulinemia. Am J Hum Genet 58:477-83
Gupta, S; Feng, L; Yoshimura, T et al. (1996) Intra-alveolar macrophage-inflammatory peptide 2 induces rapid neutrophil localization in the lung. Am J Respir Cell Mol Biol 15:656-63
Kornfeld, S J; Haire, R N; Strong, S J et al. (1996) A novel mutation (Cys145-->Stop) in Bruton's tyrosine kinase is associated with newly diagnosed X-linked agammaglobulinemia in a 51-year-old male. Mol Med 2:619-23

Showing the most recent 10 out of 48 publications