Info

designation

Chr (region)

Phenotype/function

MHC/Idd1

17 (entire H2 haplotype)

Insulitis, T1DM, diabetogenic T-cell repertoire selection, strong TH1 responses to islet antigens

Idd2

9 (Thyl)

Time of T1DM onset (T-cell activation?)

Idd3

3 (Il2)

Insulitis, T1DM

Idd5a

1 (Illrl-Vil)

Insulitis, T1DM

Idd5b

1 (Bcl2)

Peri-insulitis, sialitis, T-cell resistance to apoptosis, hypergammaglobulinemia

Idd10

3 (Tshb)

Bone marrow-derived macrophage developmental and functional defects, T1DM

Idd11

11 (Acrb-Scya-Mpo)

T-cell proliferative unresponsiveness

This chain contains 338 amino acids and, beginning from the amino terminus, is functionally divided into three regions: an extracellular hydrophilic region (amino acid residues 1-281), a transmembrane hydrophobic region (amino acid residues 282-306), and an intracytoplasmic hydrophilic region (amino acid residues 307-338). The extracellular region is further subdivided into three domains, designated a1, a2, and a3, each of approx 90 amino acid residues (see Fig. 2). The a1 and a2 domains comprise the peptide- or antigen-binding region of the molecule.

Class II HLA molecules consist of two glycoprotein chains, a-chain of approx 34 kDa and a P-chain of approx 29 kDa, both encoded within the MHC. As with the class I heavy chain, each class II chain can be divided into three regions (extracellular, transmembrane, and intracytoplasmic), but, in contrast, both class II chains span the cell membrane. Each extracellular region of the class II a- and P-chains has been further divided into two domains of approx 90 amino acid residues each, termed a1, a2 and P1, P2 respectively. The a1 and P1 domains form the peptide-binding region of class II HLA molecules (see Fig. 3). Also of note, the class II a2 and P2 domains, class I a3 domain, and P2-microglobulin all show homology to the constant region of immunoglobulins and are therefore classified as members of the immunoglobulin superfamily.

The genes that encode class I MHC are located at the HLA-A, B, and C loci, whereas class II molecules are encoded by the DR, DQ, and DP genes (see Fig. 1). Other genes in this cluster include TAP (56,57) and LMP (low-molecular-weight proteins), both involved in antigen processing (58). A third region of the MHC, denoted as class III, codes instead for several molecules having a variety of functions, namely complement components (C4A, C4B, factor B, and C2), tumor necrosis factor (TNF-a and TNF-P) and the 21-hydroxylase genes (CYP21P and CYP21) (see Fig. 1).

Whereas class I MHC molecules are expressed in virtually all nucleated cells, class II molecule expression is restricted to B-lymphocytes, dendritic cells, macrophages, and activated T-lymphocytes. Both class I and class II antigens are involved in the presentation of antigen to T-cells. Cytotoxic T-cells (CD8+) mainly recognize antigen in

HLA Region

Chromosome 6

Chromosome 6

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