Immunological dissection of human Ia molecules.

Abstract

The immunochemical analysis of Daudi Ia molecules by a variety of alloantisera led to the recognition of at least three molecular species carrying different antigenic determinants: DRw6, DC-1, and DC-2. Genetic as well as structural evidence indicates that DRw6 and DC-1 molecules are controlled by separate, HLA-linked loci, rather than by alleles at the same locus. The alloantigenic determinants appear to be expressed on the small Ia subunit. DC-1 and DC-2 determinants discussed had not been defined by serological analysis at the population level, but were demonstrated to be present by immunochemical analysis at the molecular level.

Multiple mismatches at the low expression HLA loci DP, DQ, and DRB3/4/5 associate with adverse outcomes in hematopoietic stem cell transplantation

“…HLA-DRB3/4/5, -DQ, and -DP loci, whose products are expressed at low levels, may be categorized as low expression loci (LEL). [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Examination of the distribution of HLA alleles in many world populations shows different patterns for the HEL and LEL. The HLA-A, -B, -C, and -DRB1 loci contain many alleles that are evenly distributed, and, consequently, a large proportion of the subjects of a given population are heterozygous at these loci.…”

“…The HLA loci may be classified into 2 categories according to their expression [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] or to the impact of mismatches in transplant outcome. [4][5][6][7][10][11][12][13] The HLA loci A, B, C, and DRB1 are called high expression loci (HEL), because their products are abundant on the cell surface and/or mismatches are strongly associated with transplant outcome.…”

Identification of two cis-encoded HLA-DQ molecules that carry distinct alloantigenic specificities.

“…The Ia-like antigen epitopes defined by MAb S1, R1, and Genox 3.53 show a strong association with the DR specificities l, 2, and w6, suggesting that they all detect a DQwl-like specificity (19). The molecules precipitated by all three antibodies are removed by prior exposure to an anti-DQ MAb (Leu-10) but not an anti-DR MAb (L243), indicating that all are DQ rather than DR molecules.…”

“…MAb S1 and R1 detect polymorphic B lymphocyte antigens that segregate with HLA and display biochemical characteristics of Ia-like antigens (14). Analysis of binding with a panel of cells obtained from 68 unrelated individuals revealed a strong association between the binding of these MAb and the presence of the DR antigens 1, 2, or w6 (Table I), a characteristic of the DQwl (formerly DC1) alloantigen (19). MAb Genox 3.53, which has been shown to detect the DQwl alloantigen (20), displayed a similar DR antigen association in this panel.…”

Structure of the HLA‐D Region

“…Very recently, Tosi et al made a similar immunochemical analysis of Daudi Ia molecules, and they recognized at least three molecular species carrying different antigenic determinants (14).…”