• T44
• Tp44

MAJOR LINKS FOR CD28  

• NCBI LocusLink Record: 940
• Mendelian Inheritance in Man (OMIM): 186760
• SwissProt annotated protein record: P10747

CELLULAR FUNCTION OF CD28  

• Intact anti-CD28 mAbs costimulate T cell proliferation and cytokine production with the presence of suboptimal amount of anti-CD3 mAbs, anti-CD2 mAbs or PMA in vitro
• The binding of CD28 with its ligands CD80 or CD86 costimulates T cell effector function and T cell-dependent antibody production in vitro and in vivo

DISEASE RELEVANCE OF CD28 AND FUNCTION OF CD28 IN INTACT ANIMAL  

• The blockade of CD28 signal using monoclonal antibodies against CD80 and/or CD86 or CTLA-4Ig fusion protein induces a functional inactivation of T cells in a number of in vivo experimental disease models
• CD28-deficient mice have normal T cell development and normal cell-mediated immunity but T cell-mediated humoral immunity was significantly reduced

• Families in which CD28 is a member
  • CD28-->immunoglobulin supergene family

MOLECULAR STRUCTURE OF CD28  

• Homodimeric type I transmembrane glycoprotein
• Encoded as a 220 amino acid precursor having typical features of an integral membrane protein with N-terminal signal sequence of ~27 amino acid
• The mature protein (202 amino acid) contains 134 amino acid extracellular domain with homology to an Ig V-like domain, a 27 amino acid transmembrane region and a 41 amino acid cytoplasmic tail
• The extracellular region shares significant amino acid sequence homology with CTLA-4

MOLECULAR MASS OF CD28  

POST-TRANSCRIPTIONAL MODIFICATION OF CD28  

• Four transcripts (1.3, 1.5, 3.5, and 3.7 KB) are observed in T cells
• The longer pair of transcripts (3.5/3.7 KB) is generated by the use of alternative polyadenylation signal
• The size difference between the 1.3- and 1.5-Kb and between the 3.5- and 3.7-kb is generated by internal splicing within exon 2 of extracellular domain

POST-TRANSLATIONAL MODIFICATION OF CD28  

• The extracellular region has five potential N-linked glycosylation sites
• The cytoplasmic region has a tyrosine-containing motif

SUBSTRATES FOR CD28   - No information

ENZYMES WHICH MODIFY CD28   - No information

LIGANDS FOR CD28 AND MOLECULES ASSOCIATED WITH CD28  

• Expressed, at high levels, on mature CD3+ thymocytes
• Expressed, at high levels, on most peripheral T lymphocytes
• Expressed, plasma cells (functionally unknown)

• A key challenge will be elucidation of the cellular and molecular mechanisms which distinguish the function of CTLA-4 from that of CD28, with which CTLA-4 shares amino acid sequence homology and common ligands (CD80/CD86)

SELECTION OF OTHER CD28-SPECIFIC REFERENCE MAB  

REVIEWS

1. June CH,Bluestone JA,Nadler LM,Thompson CB The B7 and CD28 receptor families. Immunol Today 1994 15:321 PubMed

2. June CH,Ledbetter JA,Linsley PS,Thompson CB Role of the CD28 receptor in T-cell activation. Immunol Today 1990 11:211 PubMed

3. Linsley PS,Ledbetter JA The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol 1993 11:191 PubMed

PRIMARY CITATIONS

4. Aruffo A,Seed B Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system. Proc Natl Acad Sci U S A 1987 84:8573 PubMed

5. Hansen JA, Martin PJ and Nowinski RC. 1980. Immunogenetics 10: 247

6. Ledbetter JA,Martin PJ,Spooner CE,Wofsy D,Tsu TT,Beatty PG,Gladstone P Antibodies to Tp67 and Tp44 augment and sustain proliferative responses of activated T cells. J Immunol 1985 135:2331 PubMed

7. Lee KP,Taylor C,Petryniak B,Turka LA,June CH,Thompson CB The genomic organization of the CD28 gene. Implications for the regulation of CD28 mRNA expression and heterogeneity. J Immunol 1990 145:344 PubMed

8. Shahinian A,Pfeffer K,Lee KP,Kundig TM,Kishihara K,Wakeham A,Kawai K,Ohashi PS,Thompson CB,Mak TW Differential T cell costimulatory requirements in CD28-deficient mice. Science 1993 261:609 PubMed

9. Weiss A,Manger B,Imboden J Synergy between the T3/antigen receptor complex and Tp44 in the activation of human T cells. J Immunol 1986 137:819 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov