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A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells.

Colonna M, Navarro F, Bellón T, Llano M, García P, Samaridis J, Angman L, Cella M, López-Botet M - J. Exp. Med. (1997)

Bottom Line: In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells.This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)-DR, respectively.In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, Basel CH-4005, Switzerland.

ABSTRACT
Natural killer (NK) cell-mediated lysis is negatively regulated by killer cell inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells. This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)-DR, respectively. In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules. These results suggest that diverse leukocyte lineages have adopted recognition of self-MHC class I molecules as a common strategy to control cellular activation during an immune response.

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Alignment of ILTs  with four Ig-SF extracellular domains. The alignment was generated by the Clustal method using  Lasergene analysis software. (DNASTAR, Inc., Madison, WI).  Amino acid sequences were  aligned with ILT2. Amino acid  variants are indicated. Gaps (dashes)  were introduced to maximize homologies. Amino acids are numbered on the right side. SS, signal  sequence; EC, extracellular domain; TM, transmembrane domain; CY, cytoplasmic domain.
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Figure 9: Alignment of ILTs with four Ig-SF extracellular domains. The alignment was generated by the Clustal method using Lasergene analysis software. (DNASTAR, Inc., Madison, WI). Amino acid sequences were aligned with ILT2. Amino acid variants are indicated. Gaps (dashes) were introduced to maximize homologies. Amino acids are numbered on the right side. SS, signal sequence; EC, extracellular domain; TM, transmembrane domain; CY, cytoplasmic domain.

Mentions: To investigate whether HP-F1 recognizes structurally distinct isoforms of ILT2, we amplified, cloned, and sequenced ILT2 cDNA from NK, T, B, and myeloid cells derived from one individual. By this approach we identified one ILT2 variant with six amino acid differences (most likely an allelic form) and two alternatively spliced forms, one of which encoded a molecule with a truncated cytoplasmic tail lacking ITIMs. (ILT2a, ILT2b, and ILT2c are available EMBL/GenBank/ DDBJ under accession numbers AF009005, AF009006, and AF009007, respectively.) These variants were not selectively expressed in different cell types. Importantly, cDNA amplification from myelomonocytic cells yielded two cDNA clones that were more diverse, called ILT4 and ILT5, also encoding glycoproteins characterized by four extracellular Ig-SF domains and ITIM-containing cytoplasmic tails (Fig. 9). These glycoproteins are homologous to ILT2 and map to human chromosome 19, but are not recognized by the HP-F1 mAb and are selectively expressed on myelomonocytic cells as assessed by RT-PCR (data not shown). These results suggest that ILT2 may be the prototype and most broadly expressed member of a family of structurally and functionally similar receptors with different MHC specificities and tissue distribution.


A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells.

Colonna M, Navarro F, Bellón T, Llano M, García P, Samaridis J, Angman L, Cella M, López-Botet M - J. Exp. Med. (1997)

Alignment of ILTs  with four Ig-SF extracellular domains. The alignment was generated by the Clustal method using  Lasergene analysis software. (DNASTAR, Inc., Madison, WI).  Amino acid sequences were  aligned with ILT2. Amino acid  variants are indicated. Gaps (dashes)  were introduced to maximize homologies. Amino acids are numbered on the right side. SS, signal  sequence; EC, extracellular domain; TM, transmembrane domain; CY, cytoplasmic domain.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199153&req=5

Figure 9: Alignment of ILTs with four Ig-SF extracellular domains. The alignment was generated by the Clustal method using Lasergene analysis software. (DNASTAR, Inc., Madison, WI). Amino acid sequences were aligned with ILT2. Amino acid variants are indicated. Gaps (dashes) were introduced to maximize homologies. Amino acids are numbered on the right side. SS, signal sequence; EC, extracellular domain; TM, transmembrane domain; CY, cytoplasmic domain.
Mentions: To investigate whether HP-F1 recognizes structurally distinct isoforms of ILT2, we amplified, cloned, and sequenced ILT2 cDNA from NK, T, B, and myeloid cells derived from one individual. By this approach we identified one ILT2 variant with six amino acid differences (most likely an allelic form) and two alternatively spliced forms, one of which encoded a molecule with a truncated cytoplasmic tail lacking ITIMs. (ILT2a, ILT2b, and ILT2c are available EMBL/GenBank/ DDBJ under accession numbers AF009005, AF009006, and AF009007, respectively.) These variants were not selectively expressed in different cell types. Importantly, cDNA amplification from myelomonocytic cells yielded two cDNA clones that were more diverse, called ILT4 and ILT5, also encoding glycoproteins characterized by four extracellular Ig-SF domains and ITIM-containing cytoplasmic tails (Fig. 9). These glycoproteins are homologous to ILT2 and map to human chromosome 19, but are not recognized by the HP-F1 mAb and are selectively expressed on myelomonocytic cells as assessed by RT-PCR (data not shown). These results suggest that ILT2 may be the prototype and most broadly expressed member of a family of structurally and functionally similar receptors with different MHC specificities and tissue distribution.

Bottom Line: In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells.This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)-DR, respectively.In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, Basel CH-4005, Switzerland.

ABSTRACT
Natural killer (NK) cell-mediated lysis is negatively regulated by killer cell inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells. This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)-DR, respectively. In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules. These results suggest that diverse leukocyte lineages have adopted recognition of self-MHC class I molecules as a common strategy to control cellular activation during an immune response.

Show MeSH
Related in: MedlinePlus