Studies on Artificial Antigens

Benacerraf, Baruj; Ojeda, Antonio; Maurer, Paul H.

doi:10.1084/jem.118.6.945

Cited by 53 publications

(14 citation statements)

References 16 publications

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“…Since R'3 has three ABA groups on a single resorcinol nucleus, it is possible that steric interference may occur at the cellular site at which the sensitized event occurs. Previous studies confirming the work of Benacerraf et al (8) demonstrated that carriers consisting of polymers of D-amino acids did not function as antigens in producing sensitization to the ABA group. It has been suggested that the failure of such carriers to function is attributable to their indigestibility by enzymes of the reficuloendothelial system.…”

Section: Resultssupporting

confidence: 69%

Immunochemical Study of Antigenic Specificity in Delayed Hypersensitivity

Leskowitz

Jones

Zak

1966

The Journal of Experimental Medicine

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Arsanilic acid conjugated to poorly antigenic carriers was shown to be capable of producing good hapten-specific delayed hypersensitivity but poor haptenspecific antibody production (1). This hapten-specific delayed hypersensitivity was only transiently suppressed by intravenous injections of monovalent conjugates of arsanilic acid and N-acetyltyrosine (2). On the other hand, intramuscular, intradermal, and intraperitoneal injections of such conjugates into newborn guinea pigs produced an unresponsiveness in respect to haptendirected delayed hypersensitivity lasting for many weeks (3). Because of this ability to produce tolerance, it became of interest to determine whether these simple monovalent conjugates could also function as complete antigens in the production of hapten-specific delayed hypersensitivity. The results demonstrate that the azobenzenearsonate (ABA) group conjugated to a variety of simple aromatic compounds is capable of acting as a complete antigen in the production of delayed hypersensitivity but rarely, if at all, in respect to antibody production.

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Section: Resultssupporting

confidence: 69%

Immunochemical Study of Antigenic Specificity in Delayed Hypersensitivity

Leskowitz

Jones

Zak

1966

The Journal of Experimental Medicine

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“…Presumably the stimulation of ABA-specific T cells by ABA-BSA might induce the release of nonspecific helper factors (10), leading to the increase observed, or two types of helper T cells like what was shown by several investigators (18,25,31) might exist. Our results with hapten conjugates of D-and i.-pclypeptides support and extend previous studies on DTH with similar materials (4,20). The failure of double conjugates of D-polymers to provide help despite their physico-chemical similarity to L-polymers suggests that they do not function as a passive bridge between T and B cell receptors.…”

Section: Discussionsupporting

confidence: 91%

Hapten‐Specific T Cell Response to Azobenzenearsonate‐N‐Acetyl‐L‐Tyrosine (ABA‐tyr) in Lewis Rats: II. Induction and Suppression of ABA‐Specific Helper Cell Activity for Antibody Production

Miyagawa

Lawn

Leskowitz

1982

Microbiology and Immunology

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Immunization of Lewis rats with azobenzenearsonate-N-acetyl-Ltyrosine (ABA-tyr) in complete Freund's adjuvant (CFA), produces a haptenspecific helper T cell response measured by an increase in plaque forming cells (PFC) against a different hapten. The response seen is primarily direct (IgM) PFC unless B cells are primed by injection of trinitrophenylated keyhole limpet hemocyanin (TNP-KLH) prior to immunization with ABA-tyr. The response requires both ABA and TNP to be on the same carrier molecule which can be as diverse as bovine serum albumin (BSA), poly L-glutamine-Iysine-tyrosine (L-GLT); however, a n-arnino acid polypeptide does not work. The in vitro demonstration of such help was successful only with peritoneal exudate lymphocytes, not spleen or lymph node cells. Repeated pretreatment of rats by intraperitoneal injection of ABA-tyr in incomplete Freund's adjuvant (IFA) induced an unresponsiveness for helper activity to subsequent immunization with the same antigen in CFA. Passive transfer of lymphoid cells from spleens and lymph nodes from rats pretreated with ABA-tyr in IFA followed by boosting with ABA-tyr in CFA induced unresponsiveness to subsequent induction of hapten-specific help.

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“…Others have also shown that polymers of D-amino acids are non-immunogenic (15)(16)(17). These findings are compatible with our previous discussion (4,5), and the concept of others that the metabolism of the antigen (18,19), previous to the formation of the immunogenic fragment carrying the antigenic determinant, is a necessary but not sufficient cri-teflon for immunogenicity. It is believed that this cleavage may be performed by proteolytic enzymes present in macrophages (20) and may be blocked by D-amino acid polymers.…”

Section: Discussionsupporting

confidence: 89%

Antigenicity of Polypeptides (Poly Alpha Amino Acids)

Maurer

1965

The Journal of Experimental Medicine

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In continuation of studies to delineate some of the criteria for immunogenicity of synthetic random polymers of a-amino acids, we have investigated the contribution of the optical configuration of the amino acids. It was hoped that by studying the immunogenicity in several species of a variety of random terpolymers containing only D-a-amino acids or mixtures of D-and L-a-amino acids, some definite conclusions could be reached concerning the role of optical configuration in immunogenicity. Previously, we reported that two polymers consisting only of the D-a-amino acids, glutamic acid, alanine, and tyrosine (G60A40, G6oA30T10) 1 were not immunogenic in rabbits or guinea pigs (1), whereas the "isomeric" polymers of L-amino acids were effective immunogens (2, 3). Moreover, the polymer G60Aa0Ti0, made of I)-amino acids, could not act as a carrier in guinea pigs for the haptene specificity of arsanilic acid (4). The polymers employed in this study were optical variations of those previously shown to be immunogenic when made of L-a-amino acids. The findings on immunogenicity will be presented here and the immunochemical relationships of the polymers will be the subject of another publication. Materials and MethodsAntigens.--Random copolymers were prepared by the polymerization of the appropriate N-carboxy-a-amino acids anhydride of the configuration indicated in Table I, by methods referred to previously (1-5). The average molecular weights were obtained from viscosity measurements as well as from measurements with the analytical ultracentrifuge. 2 Some typica] sedimentation patterns of the preparations are shown in Fig. 1.

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Studies on Artificial Antigens

Cited by 53 publications

References 16 publications

Immunochemical Study of Antigenic Specificity in Delayed Hypersensitivity

Immunochemical Study of Antigenic Specificity in Delayed Hypersensitivity

Hapten‐Specific T Cell Response to Azobenzenearsonate‐N‐Acetyl‐L‐Tyrosine (ABA‐tyr) in Lewis Rats: II. Induction and Suppression of ABA‐Specific Helper Cell Activity for Antibody Production

Antigenicity of Polypeptides (Poly Alpha Amino Acids)

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