• Kp43

MAJOR LINKS FOR CD94  

• NCBI LocusLink Record: 3824
• SwissProt annotated protein record: Q13241

• CD94/NKG2-A complex |Functions as an inhibitory receptor specific for HLA class I molecules

CELLULAR FUNCTION OF CD94  

• The CD94/NKG2-A complex is involved in inhibition of NK cell function
• The NKG2-A sequence contains cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs)
• Anti CD94 mAbs may trigger cytolytic activity and cytokine production in cells expressing the CD94/p39 complex

DISEASE RELEVANCE OF CD94 AND FUNCTION OF CD94 IN INTACT ANIMAL  

• Families in which CD94 is a member
  • CD94-->c-type lectin

MOLECULAR STRUCTURE OF CD94  

• Type II protein of 180 amino acids with a short cytoplasmic tail (7 aa)
• Extracellular C-type lectin domain
• Expressed in transfectants as a homodimer
• In NK/T cells it covalently assembles with other C-type lectin molecules (NKG2), corresponding to the kp43 and p39 subunits detected in SDS-PAGE

MOLECULAR MASS OF CD94  

• NK cells | 70 kDa | 30,43/39 kDa |The 30 kDa CD94 protein is poorly labeled with 125I. The kp43 and p39 glycoproteins detected in SDS-PAGE correspond to other C-type lectins covalently associated with CD94. See comments in [11]

POST-TRANSCRIPTIONAL MODIFICATION OF CD94   -

POST-TRANSLATIONAL MODIFICATION OF CD94  

• Two potential N-linked glycosylation sites

SUBSTRATES FOR CD94   -

ENZYMES WHICH MODIFY CD94   -

LIGANDS FOR CD94 AND MOLECULES ASSOCIATED WITH CD94  

• In NK/T cells CD94 covalently assembles with other C-type lectin molecules (NKG2), corresponding to the kp43 and p39 subunits detected in SDS-PAGE

• NK cells
• Subsets of CD8+ alpha/beta+ and gamma/delta+ T cells
• Expressed on most in vitro activated NK cells. May appear undetectable in a subset of fresh PB NK cells

• The p39 subunit is also a member of the NKG2 family
• Coexpression of the CD94/NKG2 dimers will allow a precise study of their ligand interaction
• No NKG2-specific mAbs were found in the 6th workshop panel
• The Z199 mAb specifically identifies the CD94/NKG2-A and CD94/NKG2-B dimers (Carretero et al. 1997)

SELECTION OF OTHER CD94-SPECIFIC REFERENCE MAB  

REVIEWS

1. Lopez-Botet M,Perez-Villar JJ,Carretero M,Rodriguez A,Melero I,Bellon T,Llano M,Navarro F Structure and function of the CD94 C-type lectin receptor complex involved in recognition of HLA class I molecules. Immunol Rev 1997 155:165 PubMed

2. Moretta A,Biassoni R,Bottino C,Pende D,Vitale M,Poggi A,Mingari MC,Moretta L Major histocompatibility complex class I-specific receptors on human natural killer and T lymphocytes. Immunol Rev 1997 155:105 PubMed

PRIMARY CITATIONS

3. Aramburu J,Balboa MA,Izquierdo M,Lopez-Botet M A novel functional cell surface dimer (Kp43) expressed by natural killer cells and gamma/delta TCR+ T lymphocytes. II. Modulation of natural killer cytotoxicity by anti-Kp43 monoclonal antibody. J Immunol 1991 147:714 PubMed

4. Brumbaugh KM,Perez-Villar JJ,Dick CJ,Schoon RA,Lopez-Botet M,Leibson PJ Clonotypic differences in signaling from CD94 (kp43) on NK cells lead to divergent cellular responses. J Immunol 1996 157:2804 PubMed

5. Carretero M,Cantoni C,Bellon T,Bottino C,Biassoni R,Rodriguez A,Perez-Villar JJ,Moretta L,Moretta A,Lopez-Botet M The CD94 and NKG2-A C-type lectins covalently assemble to form a natural killer cell inhibitory receptor for HLA class I molecules. Eur J Immunol 1997 27:563 PubMed

6. Chang C,Rodriguez A,Carretero M,Lopez-Botet M,Phillips JH,Lanier LL Molecular characterization of human CD94: a type II membrane glycoprotein related to the C-type lectin superfamily. Eur J Immunol 1995 25:2433 PubMed

7. Lazetic S,Chang C,Houchins JP,Lanier LL,Phillips JH Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits. J Immunol 1996 157:4741 PubMed

8. Lopez-Botet, M. 1995. In Leucocyte Typing V (ed. S.F. Schlossman et al.). Oxford University Press, Oxford, pp. 1437-39.

9. Moretta A,Vitale M,Sivori S,Bottino C,Morelli L,Augugliaro R,Barbaresi M,Pende D,Ciccone E,Lopez-Botet M,et al Human natural killer cell receptors for HLA-class I molecules. Evidence that the Kp43 (CD94) molecule functions as receptor for HLA-B alleles. J Exp Med 1994 180:545 PubMed

10. Perez-Villar JJ,Carretero M,Navarro F,Melero I,Rodriguez A,Bottino C,Moretta A,Lopez-Botet M Biochemical and serologic evidence for the existence of functionally distinct forms of the CD94 NK cell receptor. J Immunol 1996 157:5367 PubMed

11. Perez-Villar JJ,Melero I,Rodriguez A,Carretero M,Aramburu J,Sivori S,Orengo AM,Moretta A,Lopez-Botet M Functional ambivalence of the Kp43 (CD94) NK cell-associated surface antigen. J Immunol 1995 154:5779 PubMed

12. Phillips JH,Chang C,Mattson J,Gumperz JE,Parham P,Lanier LL CD94 and a novel associated protein (94AP) form a NK cell receptor involved in the recognition of HLA-A, HLA-B, and HLA-C allotypes. Immunity 1996 5:163 PubMed

13. Sivori S,Vitale M,Bottino C,Marcenaro E,Sanseverino L,Parolini S,Moretta L,Moretta A CD94 functions as a natural killer cell inhibitory receptor for different HLA class I alleles: identification of the inhibitory form of CD94 by the use of novel monoclonal antibodies. Eur J Immunol 1996 26:2487 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