PROW: CD2

PROW and IWHLDA present the GUIDE on:
CD2
Author: Kazunori Kato
Reviewer: Ellis L. Reinherz
Link to additional info in FORUM [GUIDE BAR]

ALTERNATE NAMES FOR CD2

CD2 [HUGO gene name]
CD2R
E-rosette receptor
T11
lymphocyte-function antigen-2, LFA-2

MAJOR LINKS FOR CD2

NCBI LocusLink Record: 914
Mendelian Inheritance in Man (OMIM): 186990
SwissProt annotated protein record: P06729

FUNCTION BIOCHEMICAL ACTIVITY OF CD2

CD2 primarily binds CD58 on antigen-presenting cells and induces costimulatory signals in T cells
PLC-gamma-1, p56-lck, p59-fyn, CD3zeta and CD3epsilon are tyrosine phosphorylated after CD2 stimulation

CELLULAR FUNCTION OF CD2

Critical role in alternative T cell activation
Regulatory molecule in T- or NK-mediated cytolysis
Induction of apoptosis in activated peripheral T cells
Production of cytokines by T cells
Regulation of T cell anergy

DISEASE RELEVANCE OF CD2 AND FUNCTION OF CD2 IN INTACT ANIMAL

In vivo administration of CD2 mAb or CD2 ligand (CD48) induces immunosuppression
Soluble CD58 (CD2 ligand) or anti-CD2 antibody induces sustained T cell unresponsiveness

STRUCTURE MOLECULAR FAMILY FOR CD2

Families in which CD2 is a member
- CD2-->CD2/CD48/CD58-->immunoglobulin supergene family

MOLECULAR STRUCTURE OF CD2

Single chain type I transmembrane molecule consist of 351 amino acids
CD2 has two Ig-like domains
Domain 1 resembles an Ig-V domain, although lacks the disulfide-bound
Domain 2 resembles an Ig-C2 domain
CD2 has a structural similarity and a close genetic linkage to CD58

MOLECULAR MASS OF CD2

CELL TYPE	MW UNREDUCED	MW REDUCED	Comment
Lymphocytes (T, NK)	50	50

POST-TRANSCRIPTIONAL MODIFICATION OF CD2 - No alternative splicing form

POST-TRANSLATIONAL MODIFICATION OF CD2

CD2 has three potential N-linked glycosylation sites in the extracellular region
Cross-linking of TcR/CD3 up-regulates CD2 avidity for its ligand CD58

MOLECULAR INTERACTIONS PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD2 Link to additional info in FORUM - No report

SUBSTRATES FOR CD2 - No information

ENZYMES WHICH MODIFY CD2 - No information

LIGANDS FOR CD2 AND MOLECULES ASSOCIATED WITH CD2

MOLECULE	COMMENT
CD58 (LFA-3)	Ligand, binds to CD2 domain1
CD48 (Blast1)	Ligand, binds to CD2 domain1
CD59 (HRF20)	Ligand, binds to CD2 domain1
CD15 (Lewis-x)	Ligand, bind to multimeric CD2
Sulfated carbohydrate	Ligand
CD3-zeta, epsilon chain	Associates with CD2, Brown MH et al. 1989
CD16-zeta chain	Associates with CD2, Vivier E et al. 1991
CD45	Associates with CD2, Schraven B et al. 1990
CD11a/CD18	Associates with CD2, Altin JG et al. 1994

EXPRESSION MAIN CELLULAR EXPRESSION OF CD2

Expressed almost on thymic T cells, peripheral T cells and natural killer cells
Expression on thymic B cells (approximately 50%)
Mature B cells (controversial)

AUTHOR'S ADDITIONAL INSIGHTS ON CD2

Ligand for CD2R, recognized by agonistic mAbs such as T11-3, 9.1 and L304, has not yet been identified

REAGENTS CD2-SPECIFIC MABS NEWLY ASSIGNED AT SIXTH INTERNATIONAL WORKSHOP

NAME(Workshop IDs)	SOURCE or REFERENCE	COMMENT
LT2	Filatov AV et al. 1989
MEM-65	Horejsi V (not submitted)
L303	Azuma M et al. 1992
RPA-2.10	Aversa G et al. 1987

SELECTION OF OTHER CD2-SPECIFIC REFERENCE MAB

NAME(Workshop IDs)	SOURCE or REFERENCE	COMMENT
Leu-5b	Becton Dickinson
OKT11	Ortho Diagnostic Inc.
NU-TER	Nichirei Co.
9.6	JA Hansen
39C1.5	Coulter Co.
6F10.3	Coulter Co.
9-1	K Naito
L304	M Azuma

SELECTED REFERENCES ON CD2

REVIEWS

1. Bell GM,Imboden JB CD2 and the regulation of T cell anergy. J Immunol 1995 155:2805 PubMed

2. Bierer BE,Sleckman BP,Ratnofsky SE,Burakoff SJ The biologic roles of CD2, CD4, and CD8 in T-cell activation. Annu Rev Immunol 1989 7:579 PubMed

3. Moingeon P,Chang HC,Sayre PH,Clayton LK,Alcover A,Gardner P,Reinherz EL The structural biology of CD2. Immunol Rev 1989 111:111 PubMed

PRIMARY CITATIONS

4. Arulanandam AR,Moingeon P,Concino MF,Recny MA,Kato K,Yagita H,Koyasu S,Reinherz EL A soluble multimeric recombinant CD2 protein identifies CD48 as a low affinity ligand for human CD2: divergence of CD2 ligands during the evolution of humans and mice. J Exp Med 1993 177:1439 PubMed

5. Aversa GG,Bishop GA,Suranyi MG,Hall BM RPA-2.10: an anti-CD2 monoclonal antibody that inhibits alloimmune responses and monitors T cell activation. Transplant Proc 1987 19:277 PubMed

6. Azuma M,Cayabyab M,Buck D,Phillips JH,Lanier LL CD28 interaction with B7 costimulates primary allogeneic proliferative responses and cytotoxicity mediated by small, resting T lymphocytes. J Exp Med 1992 175:353 PubMed

7. Dustin ML,Sanders ME,Shaw S,Springer TA Purified lymphocyte function-associated antigen 3 binds to CD2 and mediates T lymphocyte adhesion. J Exp Med 1987 165:677 PubMed

8. Dustin ML,Sanders ME,Shaw S,Springer TA Purified lymphocyte function-associated antigen 3 binds to CD2 and mediates T lymphocyte adhesion. J Exp Med 1987 165:677 PubMed

9. Filatov AV,Bachurin PS,Markova NA,Surnakova NE A panel of monoclonal antibodies against human lymphocyte antigens. Eksp Onkol 1989 11:28 PubMed

10. Hahn WC,Menu E,Bothwell AL,Sims PJ,Bierer BE Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand CD59. Science 1992 256:1805 PubMed

11. Kato K,Koyanagi M,Okada H,Takanashi T,Wong YW,Williams AF,Okumura K,Yagita H CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation. J Exp Med 1992 176:1241 PubMed

12. Schraven B,Wild M,Kirchgessner H,Siebert B,Wallich R,Henning S,Samstag Y,Meuer SC Alterations of CD2 association with T cell receptor signaling molecules in 'CD2 unresponsive' human T lymphocytes. Eur J Immunol 1993 23:119 PubMed

13. Warren HS,Altin JG,Waldron JC,Kinnear BF,Parish CR A carbohydrate structure associated with CD15 (Lewis x) on myeloid cells is a novel ligand for human CD2. J Immunol 1996 156:2866 PubMed

WWW RESOURCES

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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