Protein Structure and Function Lecture 6 Notes: Post-Translational Modifications Part 2 Glycosylation - Karl Landsteiner (1901) noted that blood cells from different individuals, or human blood with animal blood, would agglutinate when mixed. This agglutination phenomenon allowed him to distinguish three types of erythrocytes: A, B and C. For example, group A blood agglutinates with group B blood but never with its own type (same for group B). However, group C agglutinated with both B and C. In 1902, the blood type AB was discovered by Sturli and Von Decastello to not agglutinate with A or B. Later, Hersfeld and Freiherr von Dungern designated C as O. DONOR blood type O A B AB O A RECIPIENT blood type B AB - Landsteiner realised the agglutination was the result of an interaction between erythrocytes and a soluble component in plasma (agglutinin) now called an antibody. The immune system forms antibodies against ABO blood group antigens are not found on the individual's red blood cells. - By investigating ABO blood groups reacting with monkey and rabbit antisera, Landsteiner and Levine Anti-B Anti-A None Anti-A and Anti-B (1928) and Landsteiner and Wiener (1937, 1941) Antigens in Red Blood 1 . Cell Aantigen B antigen Aand B antigens None found that blood types can be further differentiated by other plasma antigens identified as N, M, P and Rh. The importance of the Rh factors GroupA Group B Group AB Group O Red blood cell type A B AB 0 Antibodies in Plasma became apparent from agglutination reactions in humans even when groups were matched on the ABO system. The Rh blood group, one of 35 known human blood group systems comprising over 300 antigens, is the second most important blood system. - The Rh blood system consists of 49 defined blood group antigens, among which the five antigens D, C, c, E and e are the most important. Antibodies to Rh antigens can be involved in haemolytic transfusion reactions and antibodies to the Rh(D) and Rh(c) antigens confer significant risk of haemolytic disease of the foetus/newborn. The most immunogenic and important antigen is D, and its presence/absence is noted by +/- (ergo A+, O-, etc). - Blood transfusions will generally be successful between blood of the same type. Otherwise, success will depend on whether RBCs, plasma or whole blood is being transfused. - The most common UK blood types are O+ (35%) and A+ (30%). The least common are AB- (1%) - Watkins and Morgan (1948, 1959) concluded that it is the carbohydrate structures (i.e. because glycosidase enzymes destroy/modify serological activity) that determine specificity, orientation and structural integration. - The integration suggests the RBC carries an antigen, which is type A or B, or does not (i.e. is truncated) thus is type O. Type A RBCs have a core structure involving N-acetylglucosamine, galactose and fucose, and has a non-reducing N-acetyl-a-D-galactose terminus. Type B is
very similar but has an a-D-galactose N-terminus (at carbon 2). The O determinant is missing these termini molecules and