SOME BIOCHEMICAL PROPERTIES OF THYMUS LEUKEMIA ANTIGENS SOLUBILIZED FROM CELL MEMBRANES BY PAPAIN DIGESTION

Thymus leukemia (TL) alloantigenic activity was solubilized by papain proteolytic digestion from intact RADA1 tumor cells. If the cells were labeled with amino acids and fucose, the TL alloantigen could be isolated as a doubly labeled glycoprotein fragment by indirect precipitation from the papain digest. This TL glycoprotein fragment was approximately the same mol wt as the papain-digested H-2.4 alloantigen fragment as judged by chromatography on Sephadex G-150 in sodium dodecyl sulfate. The carbohydrate chain of the TL glycoprotein obtained by exhaustive pronase digestion behaved as a glycopeptide of approximately 4,500 mol wt, as compared with the glycopeptide of the H-2.4 alloantigen that had a mol wt of about 3,500. Thus, the TL alloantigen can be solubilized by papain digestion as a glycoprotein fragment similar in mol wt to the H-2 alloantigen glycoprotein fragment. The carbohydrate chain of the TL glycoprotein is larger than the H-2 carbohydrate chain

Functional Classification of Immune Regulatory Proteins

SummaryThe members of the immunoglobulin superfamily (IgSF) control innate and adaptive immunity and are prime targets for the treatment of autoimmune diseases, infectious diseases, and malignancies. We describe a computational method, termed the Brotherhood algorithm, which utilizes intermediate sequence information to classify proteins into functionally related families. This approach identifies functional relationships within the IgSF and predicts additional receptor-ligand interactions. As a specific example, we examine the nectin/nectin-like family of cell adhesion and signaling proteins and propose receptor-ligand interactions within this family. Guided by the Brotherhood approach, we present the high-resolution structural characterization of a homophilic interaction involving the class-I MHC-restricted T-cell-associated molecule, which we now classify as a nectin-like family member. The Brotherhood algorithm is likely to have a significant impact on structural immunology by identifying those proteins and complexes for which structural characterization will be particularly informative

Unexpected complexity of the dm1 mutation revealed in the structure of three H-2D/L-related antigens

The H-2L dm1 and H-2D dm1 MHC antigens of the B10.D2 ( H-2 dm1 ) mutant mouse strain (formerly known as M504 or H-2 da ) have been compared to the H-2L d and H-2D d antigens of the B10.D2 ( H-2 d ) mouse strain. L dm1 and L d are 45 000 M r antigens and both are reactive with anti-H-2.“28” ( k/r anti- h2 ) serum and unreactive with anti-H-2.4 ( k/b anti- a ) serum which detects private determinants of the D dm1 and D d antigens. However, the tryptic peptide compositions of these two antigens are different and, based on the number of major tryptic peptides which coelute during ion-exchange chromatography, the estimated peptide homology between L dm1 and L d is 80 percent. A newly defined antigen (M r = 39 000), designated gp39 dm1 , was found in glycoprotein extracts of the dm1 strain but not of the d strain. This antigen coprecipitates with L dm1 but does not coprecipitate with D dm1 indicating that it lacks the H-2.4 determinant. In comparison with L dm1 , gp39 dm1 appears to contain far fewer Arg and Lys residues and is most likely not a simple proteolytic fragment of L dm1 . Finally, peptide maps of the D dm1 antigen show that the majority of its Arg peptides are identical to D d Arg peptides, whereas at least five of its Lys peptides and three of its Arg peptides correspond not to D d peptides but to L d and L dm1 peptides. These data raise the possibility that the D dm1 antigen is a hybrid molecule and they have also revealed an unexpected level of complexity in the dm1 mutant phenotype.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46737/1/251_2004_Article_BF00364331.pd

A global collaboRAtive study of CIC-rearranged, BCOR::CCNB3-rearranged and other ultra-rare unclassified undifferentiated small round cell sarcomas (GRACefUl)

[Background] Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of URCS patients.[Methods] URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres were retrospectively identified. Based on molecular assessment, cases were classified as follows: (1) CIC-rearranged round cell sarcomas, (2) BCOR::CCNB3-rearranged round cell sarcomas, (3) unclassified URCSs. Treatment, prognostic factors and outcome were reviewed.[Results] In total, 148 patients were identified [88/148 (60%) CIC-rearranged sarcoma (median age 32 years, range 7–78), 33/148 (22%) BCOR::CCNB3-rearranged (median age 17 years, range 5–91), and 27/148 (18%) unclassified URCSs (median age 37 years, range 4–70)]. One hundred-one (68.2%) cases presented with localised disease; 47 (31.8%) had metastases at diagnosis. Male prevalence, younger age, bone primary site, and a low rate of synchronous metastases were observed in BCOR::CCNB3-rearranged cases. Local treatment was surgery in 67/148 (45%) patients, and surgery + radiotherapy in 52/148 (35%). Chemotherapy was given to 122/148 (82%) patients. At a 42.7-month median follow-up, the 3-year overall survival (OS) was 92.2% (95% CI 71.5–98.0) in BCOR::CCNB3 patients, 39.6% (95% CI 27.7–51.3) in CIC-rearranged sarcomas, and 78.7% in unclassified URCSs (95% CI 56.1–90.6; p < 0.0001).[Conclusions] This study is the largest conducted in URCS and confirms major differences in outcomes between URCS subtypes. A full molecular assessment should be undertaken when a diagnosis of URCS is suspected. Prospective studies are needed to better define the optimal treatment strategy in each URCS subtype.This work was supported by the Carisbo Foundation Call for Translational and Clinical Medical Research.Peer reviewe