PROW: CD103

PROW and IWHLDA present the GUIDE on:
CD103
Author: Toshiyuki Tanaka
Reviewer: Nadine Cerf-Bensussan
[GUIDE BAR]

ALTERNATE NAMES FOR CD103

ITGAE [HUGO gene name]
human mucosal lymphocyte antigen 1, HML-1
integrin alphaE chain

MAJOR LINKS FOR CD103

NCBI LocusLink Record: 3682
SwissProt annotated protein record: P38570

FUNCTION BIOCHEMICAL ACTIVITY OF CD103 - No information

CELLULAR FUNCTION OF CD103

Tissue-specific retention of lymphocytes at basolateral surface of intestinal epithelial cells
Possible accessory function for activation of intraepithelial lymphocytes**

DISEASE RELEVANCE OF CD103 AND FUNCTION OF CD103 IN INTACT ANIMAL

The contribution of integrin [alpha]E[beta]7 to localization of intestinal intraepithelial lymphocytes (iIEL) was examined in integrin [beta]7-deficient mice

STRUCTURE MOLECULAR FAMILY FOR CD103

Families in which CD103 is a member
- CD103-->integrin alpha chains-->integrin assemblies

MOLECULAR STRUCTURE OF CD103

Type I transmembrane molecule (1160 amino acids: mature protein)
About 1100 amino acid extracellular domain
About 30 amino acid cytoplasmic domain
Potential divalent-cation-binding sites
Integrin I-DOMAIN (inserted domain)
X-Domain (extra domain)

MOLECULAR MASS OF CD103

CELL TYPE	MW UNREDUCED	MW REDUCED	Comment
Lymphocytes	175	150, 25

POST-TRANSCRIPTIONAL MODIFICATION OF CD103 - No information

POST-TRANSLATIONAL MODIFICATION OF CD103

The mature protein is post-translationally cleaved into the heavy fragment (about 1000 amino acids) and the light fragment (about 150 amino acids)
These components remain associated by disulfide bridge

MOLECULAR INTERACTIONS PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD103 - No information

SUBSTRATES FOR CD103 - No information

ENZYMES WHICH MODIFY CD103 - No information

LIGANDS FOR CD103 AND MOLECULES ASSOCIATED WITH CD103

MOLECULE	COMMENT
E-cadherin	Epithelial membrane protein ligand*
Integrin beta7	CD103 associates with beta subunit of heterodimer integrin alphaEbeta7

EXPRESSION MAIN CELLULAR EXPRESSION OF CD103

Expressed in more than 90% of intestinal intraepithelial lymphocytes
Expressed in about 40% of lamina propria T lymphocytes in the intestine
Expressed in the majority of intraepithelial lymphocytes present in extraintestinal sites (such as bronchi, inflammatory skin/breast/salivary glands, tumoral epitheliums)**
Expressed by 0.5-5% lymphocytes in peripheral blood and peripheral lymphoid organs*
Expressed on enteropathy-associated T cell lymphomas, hairy B cell leukemia and on adult T cell leukemias associated with HTLV-1 *
Activation and TGF-beta-1 induce CD103 expression*

AUTHOR'S ADDITIONAL INSIGHTS ON CD103

GenBank/EMBL: L25851
Useful marker for intraepithelial lymphocytes either normal or tumoral. Yet caution should be taken as overinterpretation of its expression as evidence for the intraepithelial origin of positive cells since its expression can be induced by activation and /or by TGFbeta1**
Murine homologue of alpha E: defined by M290 antibody (Kilshaw and Murant 1990; Smith et al 1994; Karecla et al 1995)**
Probable rat homologue: defined by RGL-1, RGL-2, RGL-3 antibodies (Cerf-Bensussan 1986)**
Probable chicken homologue: (Haury et al 1993)**

REAGENTS CD103-SPECIFIC MABS NEWLY ASSIGNED AT SIXTH INTERNATIONAL WORKSHOP - None

SELECTION OF OTHER CD103-SPECIFIC REFERENCE MAB

NAME(Workshop IDs)	SOURCE or REFERENCE	COMMENT
HML-1	Cerf-Bensussan N et al 1987
Ber-ACT8	Kruschwitz M et al 1991
B-ly7	Micklem KJ et al 1991
LF61	Flenghi L et al 1990
HML-2	Benmerah, A et al 1994
HML-3	Benmerah, A et al 1994
HML-4	Benmerah, A et al 1994
HML-5	Benmerah, A et al 1994
alphaE7-1	Russell GJ et al 1994
alphaE7-2	Russell GJ et al 1994
alphaE7-3	Russell GJ et al 1994

SELECTED REFERENCES ON CD103

REVIEWS

1. Shaw SK,Brenner MB The beta 7 integrins in mucosal homing and retention. Semin Immunol 1995 7:335 PubMed

PRIMARY CITATIONS

2. Benmerah A,Badrichani A,Ngohou K,Megarbane B,Begue B,Cerf-Bensussan N Homotypic aggregation of CD103 (alpha E beta 7)+ lymphocytes by an anti- CD103 antibody, HML-4. Eur J Immunol 1994 24:2243 PubMed

3. Cepek KL,Parker CM,Madara JL,Brenner MB Integrin alpha E beta 7 mediates adhesion of T lymphocytes to epithelial cells. J Immunol 1993 150:3459 PubMed

4. Cepek KL,Shaw SK,Parker CM,Russell GJ,Morrow JS,Rimm DL,Brenner MB Adhesion between epithelial cells and T lymphocytes mediated by E- cadherin and the alpha E beta 7 integrin. Nature 1994 372:190 PubMed

5. Cerf-Bensussan N,Guy-Grand D,Lisowska-Grospierre B,Griscelli C,Bhan AK A monoclonal antibody specific for rat intestinal lymphocytes. J Immunol 1986 136:76 PubMed

6. Cerf-Bensussan N,Jarry A,Brousse N,Lisowska-Grospierre B,Guy-Grand D,Griscelli C A monoclonal antibody (HML-1) defining a novel membrane molecule present on human intestinal lymphocytes. Eur J Immunol 1987 17:1279 PubMed

7. Flenghi L,Spinozzi F,Stein H,Krushwitz M,Pileri S,Falini B LF61: a new monoclonal antibody directed against a trimeric molecule (150 kDa, 125 kDa, 105 kDa) associated with hairy cell leukaemia. Br J Haematol 1990 76:451 PubMed

8. Haury M,Kasahara Y,Schaal S,Bucy RP,Cooper MD Intestinal T lymphocytes in the chicken express an integrin-like antigen. Eur J Immunol 1993 23:313 PubMed

9. Karecla PI,Bowden SJ,Green SJ,Kilshaw PJ Recognition of E-cadherin on epithelial cells by the mucosal T cell integrin alpha M290 beta 7 (alpha E beta 7). Eur J Immunol 1995 25:852 PubMed

10. Kilshaw PJ,Murant SJ A new surface antigen on intraepithelial lymphocytes in the intestine. Eur J Immunol 1990 20:2201 PubMed

11. Kruschwitz M,Fritzsche G,Schwarting R,Micklem K,Mason DY,Falini B,Stein H Ber-ACT8: new monoclonal antibody to the mucosa lymphocyte antigen. J Clin Pathol 1991 44:636 PubMed

12. Micklem KJ,Dong Y,Willis A,Pulford KA,Visser L,Durkop H,Poppema S,Stein H,Mason DY HML-1 antigen on mucosa-associated T cells, activated cells, and hairy leukemic cells is a new integrin containing the beta 7 subunit. Am J Pathol 1991 139:1297 PubMed

13. Parker CM,Cepek KL,Russell GJ,Shaw SK,Posnett DN,Schwarting R,Brenner MB A family of beta 7 integrins on human mucosal lymphocytes. Proc Natl Acad Sci U S A 1992 89:1924 PubMed

14. Russell GJ,Parker CM,Cepek KL,Mandelbrot DA,Sood A,Mizoguchi E,Ebert EC,Brenner MB,Bhan AK Distinct structural and functional epitopes of the alpha E beta 7 integrin. Eur J Immunol 1994 24:2832 ** PubMed

15. Sarnacki S,Begue B,Buc H,Le Deist F,Cerf-Bensussan N Enhancement of CD3-induced activation of human intestinal intraepithelial lymphocytes by stimulation of the beta 7-containing integrin defined by HML-1 monoclonal antibody. Eur J Immunol 1992 22:2887 ** PubMed

16. Schieferdecker HL,Ullrich R,Weiss-Breckwoldt AN,Schwarting R,Stein H,Riecken EO,Zeitz M The HML-1 antigen of intestinal lymphocytes is an activation antigen. J Immunol 1990 144:2541 PubMed

17. Shaw SK,Cepek KL,Murphy EA,Russell GJ,Brenner MB,Parker CM Molecular cloning of the human mucosal lymphocyte integrin alpha E subunit. Unusual structure and restricted RNA distribution. J Biol Chem 1994 269:6016 PubMed

18. Smith TJ,Ducharme LA,Shaw SK,Parker CM,Brenner MB,Kilshaw PJ,Weis JH Murine M290 integrin expression modulated by mast cell activation. Immunity 1994 1:393 PubMed

19. Spencer J,Cerf-Bensussan N,Jarry A,Brousse N,Guy-Grand D,Krajewski AS,Isaacson PG Enteropathy-associated T cell lymphoma (malignant histiocytosis of the intestine) is recognized by a monoclonal antibody (HML-1) that defines a membrane molecule on human mucosal lymphocytes. Am J Pathol 1988 132:1 ** PubMed

WWW RESOURCES

* indicates ammended by reviewer, ** indicates added by reviewer

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