Mechanisms of generation of antibody diversity as a cause for natural selection of homoiothermal animals in the process of evolution.
The temperature-dependence of domain interactions in the Fab, Fc, Fb and Fv fragments from human myeloma immunoglobulins (IgG) samples was investigated by scanning microcalorimetry, NMR and difference spectroscopy. The fragments were found to be very sensitive to temperature changes. Lowering the temperature below the physiological value (37 degrees C) considerably decreases the energy of interaction of the variable VH and VL domains, resulting at times in their dissociation. Since the association energies of VH and VL pairs can be affected by the result of somatic recombination and mutation events affecting antibody genes, immunoglobulins can fortuitously acquire the properties of cryoglobulins or cold autoantibodies and induce severe pathological states. It is postulated that this property of immunoglobulins, and by extension, of T-cell antigen receptors might have been one of the causes for the possible natural selection of homoiothermal animals. In these, the high conformational sensitivity of immunoglobulins to temperature change may be important in the mechanisms of induction of secondary functions in immune responses.
Zav'yalov
V P
VP
Institute of Immunology, Lyubuchany, Moscow Region, USSR.
Tishchenko
V M
VM
D000916:Antibody Diversity / Q000235:genetics*; D005075:Biological Evolution; D002152:Calorimetry, Differential Scanning; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000032:analysis; D007141:Immunoglobulin Fc Fragments / Q000032:analysis; D007135:Immunoglobulin Variable Region / Q000032:analysis; D009194:Myeloma Proteins / Q000276:immunology; D011487:Protein Conformation; D012641:Selection, Genetic; D013329:Structure-Activity Relationship; D013696:Temperature
D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007135:Immunoglobulin Variable Region; D009194:Myeloma Proteins