• L3T4
• W3/25

MAJOR LINKS FOR CD4  

• NCBI LocusLink Record: 920
• Mendelian Inheritance in Man (OMIM): 186940
• SwissProt annotated protein record: P01730

CELLULAR FUNCTION OF CD4  

• Co-receptor in MHC class II-restricted antigen-induced T cell activation (2,5)
• Regulation of T-B lymphocyte adhesion in the absence of antigen recognition (4)
• Thymic differentiation (3)
• Primary receptor for HIV retroviruses (5)

DISEASE RELEVANCE OF CD4 AND FUNCTION OF CD4 IN INTACT ANIMAL  

• Thymic differentiation
• Immune response

• Families in which CD4 is a member
  • CD4-->immunoglobulin supergene family

MOLECULAR STRUCTURE OF CD4  

• Extracellular region: 4 immunoglobulin-like domains of 370 aa
• Transmembrane region: 25 aa
• Cytoplasmic tail: 38 aa
• Disulfide bonds stabilize domains 1, 2 and 4
• Two N-linked glycans: located on domains 3 and 4
• High resolution crystal structures are available for domains 1 and 2 (9,11)

MOLECULAR MASS OF CD4  

POST-TRANSCRIPTIONAL MODIFICATION OF CD4   - No alternate splicing

POST-TRANSLATIONAL MODIFICATION OF CD4   - Two N-linked glycosylations

SUBSTRATES FOR CD4   - No information

ENZYMES WHICH MODIFY CD4   - No information

LIGANDS FOR CD4 AND MOLECULES ASSOCIATED WITH CD4  

• Thymocyte subsets
• T lymphocyte subset that recognizes antigens associated with self-MHC class II molecules
• Peripheral blood monocytes, tissue macrophages, granulocytes*

• CD4-mediated functions may require CD4 dimerization at CDR3 region of domain 1 (12) and at domain 4 (10)
• Flexibility around the transmembrane-D4 linker region (8) and the hinge region between D2 and D3 (7) may be important for HIV infection and physiological function*

SELECTION OF OTHER CD4-SPECIFIC REFERENCE MAB  

REVIEWS

1. Center DM,Kornfeld H,Cruikshank WW Interleukin 16 and its function as a CD4 ligand. Immunol Today 1996 17:476 PubMed

2. Gaubin M,Autiero M,Houlgatte R,Basmaciogullari S,Auffray C,Piatier-Tonneau D Molecular basis of T lymphocyte CD4 antigen functions. Eur J Clin Chem Clin Biochem 1996 34:723 PubMed

3. Kisielow P,von Boehmer H Development and selection of T cells: facts and puzzles. Adv Immunol 1995 58:87 PubMed

4. Mazerolles F,Auffray C,Fischer A Down regulation of T-cell adhesion by CD4. Hum Immunol 1991 31:40 PubMed

5. Sattentau QJ,Weiss RA The CD4 antigen: physiological ligand and HIV receptor. Cell 1988 52:631 PubMed

PRIMARY CITATIONS

6. Autiero M,Cammarota G,Friedlein A,Zulauf M,Chiappetta G,Dragone V,Guardiola J A 17-kDa CD4-binding glycoprotein present in human seminal plasma and in breast tumor cells. Eur J Immunol 1995 25:1461 PubMed

7. Brady RL,Dodson EJ,Dodson GG,Lange G,Davis SJ,Williams AF,Barclay AN Crystal structure of domains 3 and 4 of rat CD4: relation to the NH2- terminal domains. Science 1993 260:979 PubMed

8. Moir S,Perreault J,Poulin L Postbinding events mediated by human immunodeficiency virus type 1 are sensitive to modifications in the D4-transmembrane linker region of CD4. J Virol 1996 70:8019 PubMed

9. Ryu SE,Kwong PD,Truneh A,Porter TG,Arthos J,Rosenberg M,Dai XP,Xuong NH,Axel R,Sweet RW,et al Crystal structure of an HIV-binding recombinant fragment of human CD4. Nature 1990 348:419 PubMed

10. Sakihama T,Smolyar A,Reinherz EL Oligomerization of CD4 is required for stable binding to class II major histocompatibility complex proteins but not for interaction with human immunodeficiency virus gp120. Proc Natl Acad Sci U S A 1995 92:6444 PubMed

11. Wang JH,Yan YW,Garrett TP,Liu JH,Rodgers DW,Garlick RL,Tarr GE,Husain Y,Reinherz EL,Harrison SC Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains. Nature 1990 348:411 PubMed

12. Zhang, X., D. Piatier-Tonneau, C. Auffray, R. Murali, A. Mahapatra, F. Zhang, C. C. Maier, H. Saragovi, and M. I. Greene. 1996. Nature Biotechnology 14: 472-475.

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