This document summarizes the structure and functions of red blood cell membranes and antigens. It discusses how antigens are borne on membrane proteins and lipids, and their roles in membrane integrity, gas exchange, and structural support. It also describes several blood group systems (ABO, Rh, Kell, Diego, Colton, Kidd), the transport proteins and receptors they are located on, and their functions in adhesion, complement regulation, and interactions with viruses and bacteria. Deficiencies in various antigens can cause hemolytic anemias or shape abnormalities due to impacts on membrane structure.

1. Red cell membrane and
antigen functions
DR. G.D.A. SAMARANAYAKA

2. SDS-polyacrylamide gel electrophoresis of human red blood cell (RBC) membranes. Healthy human
RBC membranes stained with periodic acid-Schiff (PAS) stain

3. Red cell membrane structure

4. Schematic representation of the red cell membrane showing antigen-bearing glycosylation of
proteins and lipids GPI = glycophosphatidylinositol

5. Biosynthesis of
antigens of the
ABO, Ii, P and
Lewis systems

6. Red cell antigen functions

7. Blood group antigens on molecules
important to membrane integrity
Leach phenotype (absence of all Gerbich antigens).
 Caused by total deficiency of glycophorins C and D
 deficient in one or more of high frequency Gerbich antigens cause red cell shape
abnormalities
Rhnull phenotype
 mild hemolytic anemia with stomatocytosis and spherocytosis
McLoad phenotype
 protein product of the Xk gene (Kx protein) is absent
 acanthocytic red cells as well as a mild hemolytic anemia

8. Blood group antigens on molecules
important to membrane integrity
Deficiency of band 3
 Band 3 protein is the most abundant red cell membrane protein.
 AE1 (anion channel protein) is the product of the Di locus (Diego)
 Determinants of the Di blood group system are associated with amino
acid substitutions with band 3
 Found in red cells and intercalate cells of distal and collecting tubules
 Crucial role in O2/CO2 gas exchange between lungs and tissues.
 structural functions by interacting with skeletal proteins.
 Deficiency of band 3 in the red cells has been considered to be lethal &
no Diego-null phenotype is reported

9. Transport protein
Kell antigens
 Closely related to endothelin converting enzymes
 Kxa - membrane transporter structure – McLeod
 >20 kell antigens located on lymphocytic leukemia antigen (CALLA)
Dombrock antigens
 Located on a glycosylphosphatidylinositol-linked protein
Diego system
 on band 3 or the anion channel protein (AE1)
Colton antigens
 Coa- Cob and Co3
 On a channel-forming integral protein aquaporin-1
Kidd
 urea transporter
 expressed in the endothelial cells of the renal vasarecta and the medulla

10. Adhesion receptors
 Members of the immunoglobulin glycoprotein super family (IgSF)
 characterized by repeating extracellular domains with sequence
homology to the variable (V) and constant (C1 or C2) domain of
immunoglobulins.
 Lutheran blood group antigens (CD 23q) - lamini receptor on both
sickle red cells as well as many epithelial cancers
 LW protein (ICAM-4 CD24q) – bind integrins (CD11/CD18)
 Ina and Inb CD44 - leukocyte homing receptor and adhesion molecule.

11. Receptor function
DARC (Duffy antigen receptor for chemokines).
 Bind - IL-8 and MCP-1.
 principally found on lymphocytes.
 receptor for the malarial parasite P
. vivax.

12. Complement-related function
Knops/McCoy blood group antigen.
 It is the C3b/C4b receptor aka complement receptor type 1 (CR1).
 important in immune adherence.
Decay accelerating factor (DAF/CD55) & Membrane inhibitor
of reactive lysis proteins (MIRL-CD59).
 Both CD55 and CD59 are attached to the membrane by.
glycosylphosphatidylinositol anchors (GPI-AP).
 Associated with paroxysmal nocturnal hemoglobinuria (PNH).

13. Receptors on viruses and bacteria
 Many bacteria strains bind to a galactose-α1 -motif shared by the
blood group antigens P
, Pk and P1 and are responsible for enteral and
upper urinary tract infections.
 Glycoconjugates carrying Lewisa specificity bind B pertussis and
staphylococcus aureus toxins.
 The receptor of parvovirus B19 is the P glycolipid (globoside) on the
surface of erythroid progenitors.
 DAF (CD55) functions as receptor for the DR. family of adhesions
from E. coli strains – UTI.

14. References
 A Comprehensive Review of Our Current Understanding of Red
Blood Cell (RBC) Glycoproteins - by Takahiko Aoki
 Red cell antigens: Structure and function - Abbasali Pourazar

15. Thank You