Richard M. Krause

The search for antibodies with molecular uniformity.

Publisher Summary This chapter discusses the physical, chemical, and biological aspects of γM antibodies in depth. The chapter describes the physical characteristics, chemical composition, and subunit structure of the typical circular γM pentomers and the relationship of these molecules to low molecular weight γM-like proteins. The characteristics of the interaction of γM antibodies with antigens—for example, the nature and number of antigen combining sites—and the interaction of γM antibodies with the complement system are compared to the corresponding properties of γG antibodies. The biosynthesis and metabolism of γM antibodies and their peculiar role in the immune response are also discussed in the chapter. The chapter presents a brief summary related to the hallmarks of immunoglobulin heterogeneity and the criteria that must be used to judge the restricted heterogeneity or molecular uniformity of an antibody preparation. The chapter discusses human antibodies to certain selected antigens that appear to possess less heterogeneity than normal γ-globulin.

Summary of antibody workshop: The Role of Humoral Immunity in the Treatment and Prevention of Emerging and Extant Infectious Diseases.

In the era before antibiotics, human diseases were commonly treated with immune animal and human sera, often with life-saving results. With the advent of emerging infectious diseases, many of which cannot be adequately treated or prevented, attempts to develop antibody treatments have taken on new importance. The role of humoral immunity in treatment and prevention was the focus of discussion at a 1996 workshop. The cellular and molecular mechanisms of neutralization were examined in detail. It was noted that success in passive immunity has frequently been the key element in devising a successful strategy to develop a vaccine for active immunization. The workshop concluded on a cautious note of optimism that antibody-based treatment and prevention for diseases such as human immunodeficiency virus infection, Ebola fever, and others of clinical and public health importance deserve further development and clinical trial.

INTRODUCTION TO SESSION ON HOMOGENEOUS ANTIBODIES

In these introductory remarks I am disinclined to review in any formal sense the recent history which brings us to a consideration of homogeneous antibodies and myeloma proteins with antibody activity. It should, perhaps, not go unnoticed that devoting a special section of a conference to this subject is a recent development, but it is one which I believe will be short-lived. In a sense, special sessions such as this one are a testimony to our surprise that, on the one hand, antibodies were not necessarily unmanageable mixtures; and on the other hand, that myeloma proteins had the potential to behave like respectable antibodies. Certainly there is nothing more respectable than combining with DNP! I believe that special sessions on this general subject will be a transient phenomenon because attention will turn from scepticism about the homogeneity of antibodies and the antibody nature of myeloma proteins, and will focus rather on the uses and abuses of these proteins. Antibodies to microbial carbohydrates, for example, are workable substitutes for the myeloma proteins in the rabbit, a species in which myeloma has not thus far been observed as a natural occurrence. We will learn from Dr. Eisen, later in this monograph, the remarkable way in which the antibody activity of certain proteins resembles that of bonafide antibodies. Therefore, let me suggest to all future conference organizers that our special section be permitted to lapse. The time is close at hand for the workers who employ these special proteins to be assigned to other sections of symposia which deal with antibody structure, the combining site, immunogenetics, and the mechanisms which manufacture antibody diversity. I would stress, however, that this in no way implies that some of us who are preoccupied with antibodies to carbohydrates will stand in the wings waiting for the end. This is not the end of an affair because antibodies to carbohydrates, recognized in the historical past by Avery and Heidelberger as the front line of defense against disease, were reexamined again in the sixties for their protective powers. The participants in this session have dealt with two major questions for the past few years. First: do specific antibodies under special circumstances have a molecular uniformity which mimics that of the myeloma proteins? Stated another way: can homogeneous antibodies be obtained experimentally in a reproducible and predictable fashion? The second question concerns the discovery of antibody activity for myeloma proteins and paraproteins. This discovery has raised the cautious question: is such a protein, which reacts with specific antigen, a genuine prototype of a specific antibody directed against the same antigen? The decade just past began with the first indication, as described by Kritzman and associates,l that paraproteins had definable antibody activity. It was

A peptide mapping technique--a three map system.

Abstract A high resolution peptide mapping system has been described. The method utilizes three maps for separation of the acidic, basic, and neutral constituents of a proteolytic digest of a protein. Peptides from a proteolytic digest are separated by electrophoresis at pH 6.5 into acidic, basic, and neutral peptides. The secondddimensional electrophoresis is performed at pH 2.1 for each of acidic peptides and basic peptides. The third map is prepared from the neutral peptides. For this map, paper chromatography was used for the first dimension and electrophoresis at pH 2.1 for the second dimension.

Immune response deficiency of bsvs mice. I. Identification of ir gene differences between a/j and bsvs mice in the antistreptococcal group a carbohydrate response.

The genetic control of the low response of BSVS mice to streptococcal Group A carbohydrate (GAC) was studied in crosses with responder A/J mice. F1 mice were responders. In the backcross (BSVS × A/J)F1 × BSVS mice, there were equal numbers of anti-GAC responder and nonresponder mice, indicating genetic control by a small number of major loci. The anti-GAC responses of the backcross mice showed no obligate linkage between responder status and A/JH-2 orIgCH alleles. However, it was observed that the average anti-GAC titers were higher in backcross mice heterozygous at these loci. The above data, a lack of low-responder F2 animals, and the segregation of a non-H-2-, non-IgCH-linked locus in the first and second backcross mice, indicate that the defect in the BSVS anti-GAC responsiveness involves three loci: one linked toH-2, another linked toIgCH, and a third locus —tentatively namedIr-GAC- not linked toH-2, IgCH, orHbb.

PREVENTION OF STREPTOCOCCAL PHARYNGITIS AMONG MILITARY PERSONNEL AND THEIR CIVILIAN DEPENDENTS BY MASS PROPHYLAXIS.

MANY studies have described the incidence of streptococcal pharyngitis in military personnel,1 , 2 and more recently attention has been focused on the occurrence of this disease in nonmilitary popu...