HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schreiber, R. D. Articles by Reichlin, M. Search for Related Content PubMed Articles by Schreiber, R. D. Articles by Reichlin, M.

Restriction of Heterogeneity of Goat Antibodies Specific for Human Hemoglobin S¹

Departments of Medicine and Biochemistry, State University of New York at Buffalo School of Medicine, Veteran's Administration Hospital, Buffalo, New York

Abstract

Previously, we had reported the isolation of an antibody population (termed antiVal antibody) specific for the site of difference between human hemoglobin S (HbS) (⁶Val) and hemoglobin A₁ (HbA) (⁶ glu). This population has a stoichiometry of reaction of unity in combining with HbS ( dimer) and shows no reaction with HbA. The combination of antiVal Fab fragments with HbS was found to be kinetically homogeneous and had a second order rate constant of 0.58 x 10⁶M^-1 sec^-1 at 20°C. In this report we have studied other properties of the antiVal population. These antibodies are restricted to only one of the two heavy chain subclasses of goat IgG. Electrophoresis experiments indicated that the antiVal population is much less polydisperse than the total antiHbS response. A method was developed to measure the dissociation kinetics of antiVal-HbS complexes. This dissociation was also found to be kinetically homogeneous and could be described by a single first order rate constant of 2.67 x 10 ⁵sec ¹at 20°C. With homogeneous association and dissociation rate constants, an affinity constant of 2.1 x 10¹⁰M^-1 at 20°C was calculated. It appears, then, that this population of antibodies, which are directed toward a single antigenic determinant on a globular protein, exhibit limited structural heterogeneity associated with great functional homogeneity.

Footnotes

¹ This research was supported by Grant HE 12524 from the National Heart and Lung Institute, National Institutes of Health, Funds for Veteran's Administration Research Project 6098-01, by designated research funds from the Veterans' Administration, and Grant AM10428 from the United States Public Health Service.

² This work was done in partial fulfillment of the degree of doctor of philosophy from the graduate school of SUNY at Buffalo, supported by predoctoral fellowship United States Public Health Service GM46140. Reprint requests should be sent to R.S., Scripps Clinic and Research Foundation, 476 Prospect Street, La Jolla, California 92037.

³ R.W.N. is an established investigator of the American Heart Association.