Major alloantigenic systems Blood group antigens

Hundreds of blood group antigens have been identified by red blood cell serology. The well-known major blood group alloantigenic systems (ABO(H), Rh) are very important from a clinical standpoint. The minor blood group systems (e.g. Lewis, MNS, Lutheran, Kell, Duffy, Kidd, P, I) also are clinically significant, but less so. The Rh system is one of the most polymorphic antigen systems known, as it comprises at least 50 antigens, all of which are encoded by alleles at either of two loci, D or CcEe; the D antigens are the most immunogenic of all the red blood cell antigens. The MNS system is also highly

Table 1 Major alloantigenic systems with their basic functions and clinical significance

1. Blood group antigens Major systems: ABO(H), Rh

Minor systems: Lewis, MNS, Lutheran, Kell, Duffy, Kidd

Functional and clinical significance: blood transfusion, tissue or organ transplantation, hemolytic diseases and inflammatory responses

2. Histocompatibility antigens

A. Major Histocompatibility antigens (MHC)

(a) Classical

Class I: Human H LA-A, B, C Mouse H2-K, D, L Rat RT1 .A, F, E Class II: Human H LA-DP, DQ, DR Mouse H2-A, E Rat RT1 .H, B, D

Functional and clinical significance: presentation of antigenic peptides to T cells; association with susceptibility to a number of diseases; tissue and organ transplantation

(b) Nonclassical:

Class I: Human HLA-E, F, G, H, J, K, L; MIC (MHC class I chain related) Mouse H2-Q, T, M Rat RT1 .C, K, G, O, N, M Class II: Human H LA-DMA, DMB Mouse Ma, Mb,, Mb2

Functional and clinical significance: presentation of specific antigenic peptides to T cells; DMA/DMB act as accessory molecules in antigen presentation by class II antigens.

(c) MHC class III antigens

Human: C2, factor B (Bf), C4A and C4B (complement proteins); TNFcx, TNFp (tumor necrosis factors); steroid 21-

hydroxylase (CYP21); major 70 kDa stress protein Hsp70; and TAP (transporter of antigenic peptides) Mouse C2, C4, Bf, Sip (sex-limited protein), 21-hydroxylase (21-OH), Hsp70 and TNFcx, TNFp Rat C2, C4, Bf, Hsp70, Cyp21, TAP, TNFcx

Functional and clinical significance: complement functions; transport of antigenic peptides; chaperones in antigen processing and presentation

(d) MHC-like antigens encoded by genes residing outside the MHC Class l-like

Human, mouse, rat: FcRn Human, mouse, rat: CD1 Human: Zinc «¡.-glycoprotein (ZAG) Functional and clinical significance: FcRn binds IgG from ingested milk from mother and transfers it across intestinal cells to the bloodstream; CD1 predominantly presents nonpeptide lipid and glycolipid antigens to T cells: and ZAG has no known physiological function

B. Minor histocompatibility antigens

(b) Many tissue-specific antigens in all species

(c) Mis endogenous superantigens

Mouse: Mls-1a, Mls-2a, Mls-3a Functional and clinical significance: slow tissue rejection, mixed lymphocyte stimulation

3. Differentiation antigens (CD)

In excess of 100 clusters have been identified in humans Functional and clinical significance: Involved in cellular interactions.

complex, comprising two closely linked homologous genes GYPA and GYPB, that encode for at least 38 antigens. Recent studies at the molecular level indicate that a variety of genetic mechanisms gives rise to this complexity. So far, Rh antigens have been detected only on red blood cells, but the ABO(H), Lewis, P and I antigens are widely distributed throughout the body. Recent data suggest functional roles for blood group antigens unrelated to erythrocytes: cell adhesion, association with diseases, tumor markers and receptors for parasites, bacteria and viruses.

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