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1. Repeated large infusions of heterologous plasma proteins can induce a state of specific immunologic unresponsiveness in rabbits. In normal adult rabbits this unresponsiveness in most instances lasts only about as long as the heterologous proteins are detectable in the host (3 to 4 months). In rabbits infused from the time of birth and perhaps x-radiated adult rabbits the induced immunologic unresponsiveness lasted throughout the period of observation (10 to 11 months), long after disappearance of all detectable foreign proteins. 2. This unresponsiveness appears to be specific for the antigens administered in excess and does not prevent antibody responses to even closely related antigens. 3. The unresponsiveness was not transmitted to first generation offspring. 4. The mechanism of the temporary unresponsiveness which occurs in normal adult rabbits may be dependent upon the actual presence of the antigen in the host. However, the unresponsiveness does not result from a simple neutralization of antibody, as it is formed, by the antigen, as has been suggested in the case of pneumococcal polysaccharide induced immunologic paralysis. 5. On the other hand, the mechanism of the lasting immunologic unresponsiveness developing in the "newborn" and perhaps the x-rayed rabbits may depend upon the acceptance of the foreign protein as essentially non-antigenic by the host. A similar situation is seen in the naturally occurring placental transfer of dissimilar red blood cell types between fraternal twins.

It has been shown that the half-lives of homologous gamma globulins vary from species to species ( 1 ) . As a corollary, the half-lives of homologous serum albumins have been determined using the protein label, a convenient tool for the measurement of protein catabolism.Materials and methods. Albumin was separated from human, bovine, and rabbit serum in the laboratories of Armour and Co. according to the alcohol fractionation procedure of Cohn(2). Albumin from dog and mouse serum was obtained by electrophoretic separation in a Tiselius apparatus in the laboratory of Dr. D. H. Moore of Columbia University. To the albumins in a pH seven 0.2 M phosphate buffer was added a slightly acid solution of 1l3l as free iodine and then the pH of the mixture was raised to 9 by the addition of 0.1 N NaOH. Non-protein-bound iodine was eliminated by dialysis against refrigerated tap water for 72 hours. The entire procedure was carried out at Oo-5" C. Final preparations contained less than one iodine atom per molecule of protein and at least 99% of the radioactivity was protein bound, as determined by trichloracetic acid precipitation. (1) The following subjects were used: Eleven men ages 23 to 75 who were institutionalized in a county 'home. These men had the following diagnoses: 5multiple sclerosis, 2hemiplegia old, onehealed osteomyelitis, onechronic arthritis, onepost operative bladder cancer, and oneasthma. ( 2 ) Three nonlactating full grown Swiss and Jersey cows.(3) Nine full grown mongrel dogs. (4) Nine young albino male rabbits weighing between 2 and 2.2 kg for rabbit albumin half-life determination. ( 5 ) Eight young albino male rabbits weighing between 2 and 2.2 kg for the determination of the effect of mekabolic rate on albumin half-life. (6) Thirty young adult CFW

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.

In previous studies reported in this series of papers, we have shown that histoincompatible mouse carrier-primed T lymphocytes fail to provide the required stimulus for the responses of B cells to hapten-carrier conjugates (1-3). Utilizing a system designed to eliminate nonspecific T cell influences from potential development of an "allogeneic" effect (reviewed in references 4 and 5), mixtures of suitably primed T and B lymphocytes from histoincompatible donors failed to cooperate effectively in developing anti-2,4-dinitrophenyl (DNP) antibody responses either in vivo or in vitro (2, 3). Moreover, experiments carried out in congenic-resistant mouse strains have provided conclusive evidence that a gene or genes present in the H-2 complex control (s) the capacity of antigen-specific T and B cells to effectively interact (3).In this report, we present results of experiments designed to question the role of the immune response (Ir) genes and their product(s) in the control of physiologic, i.e. antigen-specific, T-B cell cooperative interactions. This has been accomplished by taking advantage of our previous demonstration of highly effective cooperation between reciprocal combinations of parental and Fz hybrid T and B lymphocytes when the carrier molecule employed is one to which both parental strains are genetic responders (2). We now have asked the question of whether F1 carrier-primed T cells can serve as helper cells for either or both parental B cells when (a) the carrier molecule employed is under genetic control such that one parental strain is a responder and the other is a nonresponder, and (b) the determinant specificity of the parental B cells being assessed is not under genetic control and bears no relationship to the specificity of the carrier molecule. The experimental system utilizes an immune response gene controlling responses to the terpolymer L-glutamic acid-L-lysine-Ltyrosine (GLT) to which A strain mice (1f-2 ~) are nonresponders whereas BALB/c (H-2 ~) and (BALB/c X A)F1 hybrids (CAFI) are respondcrs. 1 These studies demonstrate that GLT-primed T ceils of CAF~ donors can provide for responder BALB/c,