Disease relevance of LY9

• The cytoplasmic tail of CD229 binds to SAP, a protein that is defective in X-linked lymphoproliferative syndrome [1].
• Human Ly9 (CD229) as novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (B-CLL) recognized by autologous CD8+ T cells [2].

High impact information on LY9

• Interestingly, the CD229 mutant lacking the Grb2 binding site is not internalized after CD229 engagement with specific Abs [3].
• Confocal microscopy image analysis revealed relocalization of CD229 to the contact area of T and B cells during Ag-dependent immune synapse formation [1].
• CD229 is a lymphocyte cell surface molecule that belongs to the CD150 family of receptors [3].
• Unexpectedly, Erk phosphorylation was partially inhibited after activation of CD229 plus CD3 [3].
• Moreover, a dominant negative form of Grb2 (containing only Src homology 2 domain) impaired CD229 endocytosis [3].

Biological context of LY9

• Identification of Grb2 as a novel binding partner of the signaling lymphocytic activation molecule-associated protein binding receptor CD229 [3].
• OBJECTIVE: CD229, a cell-surface molecule being involved in cell adhesion, is overexpressed in B-CLL cells [2].

Anatomical context of LY9

• Mutant T53I, however, did not bind to CD229 and CD224, suggesting that SH2D1A controls several critical signaling pathways in T and natural killer cells [4].
• CD229 presented a pattern of expression restricted to lymphocytes [5].
• Moreover, CD229 binds to the AP-2 complex in T and B cell lines, and it is internalized rapidly from the cell surface on T cells after antibody ligation [6].
• CD229 (Ly9) is a cell surface receptor selectively expressed on T and B lymphocytes, and it belongs to the CD150 receptor family [6].
• Consistent with this, CD229 ligation partially inhibited TCR signaling in peripheral blood cells and CD229-Jurkat cells transfected with the 3XNFAT-luciferase reporter construct [3].

Associations of LY9 with chemical compounds

• Upon tyrosine phosphorylation, CD229 recruits various signaling molecules to the membrane [3].
• CD229-CD229 binding was severely compromised when the charged amino acids E27 and E29 on the predicted B-C loop and R89 on the F-G loop of the N-terminal domain were mutated to alanine [1].

Physical interactions of LY9

• We report that CD229 interacts in a phosphorylation-dependent manner with Grb2 [3].

Regulatory relationships of LY9

• The number of CD8+ T cells could be expanded during 4 weeks of in vitro culture with native or CD40L-activated B-CLL cells while the amount of specific T cells recognizing CD229 peptides bound to HLA-A2 dimers increased on average 12-fold (native CLL) and 13-fold (CD40L-activated CLL), respectively [2].

Other interactions of LY9

• Two residues in the beta 2 domain, beta 180 and beta 181, were also shown to be involved in the epitopes of three polymorphic anti-DR mAbs, NFLD.D1, NFLD.M1, and LY9 [7].
• PATIENTS AND METHODS: Autologous, CD229-specific HLA-A2-restricted T cells were identified using IFN-gamma-ELISPOT assays and HLA-A2/dimer-peptide staining after 4 weeks of in vitro culture [2].

References